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Endocannabinoids and Lipid Mediators in Brain Functions pp 319–346Cite as

Roles of N-Acylethanolamines in Brain Functions and Neuropsychiatric Diseases

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Abstract

N-acylethanolamines (NAEs) are bioactive lipids, structural analogues to the endocannabinoid arachidonoylethanolamide (anandamide), whose functions and properties are being elucidated in recent years. By activating their receptors, specifically peroxisome proliferator-activated receptors (PPARs), these molecules exert a variety of physiological effects via genomic and rapid non-genomic mechanisms. Regulation of lipid metabolism, energy homeostasis, and anti-inflammation are among the best-characterized effects of PPAR activation. NAEs are abundant in the CNS and their receptors are widely expressed both in neurons and in glial cells, where they modulate brain functions and are involved in the pathophysiology of neurological and psychiatric disorders. In the brain, they participate in the regulation of feeding behavior, cognitive functions, mood, reward, and sleep-wake cycles, and evidence suggests that they might be therapeutically exploited as neuroprotective agents, “anti-addictive” medications, anticonvulsant, and antidepressant.

In this chapter, we will review the state of the art on these neuromodulators and their receptors in the brain and will discuss new hypotheses on their physiological and pathophysiological roles.

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References

  • Adamczyk P, Golda A, McCreary AC, Filip M, Przegalinski E (2008) Activation of endocannabinoid transmission induces antidepressant-like effects in rats. J Physiol Pharmacol 59(2):217–228

    CAS  PubMed  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub

    Google Scholar 

  • Ascherio A, Munger KL (2016) Epidemiology of multiple sclerosis: from risk factors to prevention-an update. Semin Neurol 36(2):103–114. doi:10.1055/s-0036-1579693

    Article  PubMed  Google Scholar 

  • Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H (1997) Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 46(8):1319–1327

    Article  CAS  PubMed  Google Scholar 

  • Auvin S (2012) Fatty acid oxidation and epilepsy. Epilepsy Res 100(3):224–228. doi:10.1016/j.eplepsyres.2011.05.022

    Article  CAS  PubMed  Google Scholar 

  • Avagliano C, Russo R, De Caro C, Cristiano C, La Rana G, Piegari G, Paciello O, Citraro R, Russo E, De Sarro G, Meli R, Mattace Raso G, Calignano A (2016) Palmitoylethanolamide protects mice against 6-OHDA-induced neurotoxicity and endoplasmic reticulum stress: In vivo and in vitro evidence. Pharmacol Res 113(Pt A):276–289. doi:10.1016/j.phrs.2016.09.004

    Article  CAS  PubMed  Google Scholar 

  • Bachur NR, Masek K, Melmon KL, Udenfriend S (1965) Fatty acid amides of ethanolamine in mammalian tissues. J Biol Chem 240:1019–1024

    CAS  PubMed  Google Scholar 

  • Baker D, Pryce G, Davies WL, Hiley CR (2006) In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol Sci 27(1):1–4. doi:10.1016/j.tips.2005.11.003

    Article  CAS  PubMed  Google Scholar 

  • Balenga NA, Aflaki E, Kargl J, Platzer W, Schroder R, Blattermann S, Kostenis E, Brown AJ, Heinemann A, Waldhoer M (2011) GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res 21(10):1452–1469. doi:10.1038/cr.2011.60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bensinger SJ, Tontonoz P (2008) Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454(7203):470–477. doi:10.1038/nature07202

    Article  CAS  PubMed  Google Scholar 

  • Berger J, Moller DE (2002) The mechanisms of action of PPARs. Annu Rev Med 53:409–435

    Article  CAS  PubMed  Google Scholar 

  • Bilbao A, Serrano A, Cippitelli A, Pavon FJ, Giuffrida A, Suarez J, Garcia-Marchena N, Baixeras E, Gomez de Heras R, Orio L, Alen F, Ciccocioppo R, Cravatt BF, Parsons LH, Piomelli D, Rodriguez de Fonseca F (2015) Role of the satiety factor oleoylethanolamide in alcoholism. Addict Biol. doi:10.1111/adb.12276

    Google Scholar 

  • Blednov YA, Benavidez JM, Black M, Ferguson LB, Schoenhard GL, Goate AM, Edenberg HJ, Wetherill L, Hesselbrock V, Foroud T, Harris RA (2015) Peroxisome proliferator-activated receptors alpha and gamma are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcohol Clin Exp Res 39(1):136–145. doi:10.1111/acer.12610

    Article  CAS  PubMed  Google Scholar 

  • Blednov YA, Black M, Benavidez JM, Stamatakis EE, Harris RA (2016) PPAR Agonists: II. Fenofibrate and Tesaglitazar Alter behaviors related to voluntary alcohol consumption. Alcohol Clin Exp Res 40(3):563–571. doi:10.1111/acer.12972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bornheim LM, Kim KY, Chen B, Correia MA (1993) The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism. Biochem Biophys Res Commun 197(2):740–746

    Article  CAS  PubMed  Google Scholar 

  • Bortolato M, Mangieri RA, Fu J, Kim JH, Arguello O, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2007) Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry 62(10):1103–1110. doi:10.1016/j.biopsych.2006.12.001

    Article  CAS  PubMed  Google Scholar 

  • Bough KJ, Rho JM (2007) Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 48(1):43–58. doi:10.1111/j.1528-1167.2007.00915.x

    Article  CAS  PubMed  Google Scholar 

  • Bough KJ, Schwartzkroin PA, Rho JM (2003) Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo. Epilepsia 44(6):752–760. doi:55502 [pii]

    Article  PubMed  Google Scholar 

  • Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W (1996) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137(1):354–366

    Article  CAS  PubMed  Google Scholar 

  • Brundin P, Wyse R (2015) Parkinson disease: laying the foundations for disease-modifying therapies in PD. Nat Rev Neurol 11(10):553–555. doi:10.1038/nrneurol.2015.150

    Article  CAS  PubMed  Google Scholar 

  • Campolongo P, Roozendaal B, Trezza V, Cuomo V, Astarita G, Fu J, McGaugh JL, Piomelli D (2009) Fat-induced satiety factor oleoylethanolamide enhances memory consolidation. Proc Natl Acad Sci U S A 106(19):8027–8031. doi:10.1073/pnas.0903038106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carta AR (2013) PPAR-gamma: therapeutic prospects in Parkinson’s disease. Curr Drug Targets 14(7):743–751

    Article  CAS  PubMed  Google Scholar 

  • Chase KA, Rosen C, Gin H, Bjorkquist O, Feiner B, Marvin R, Conrin S, Sharma RP (2015) Metabolic and inflammatory genes in schizophrenia. Psychiatry Res 225(1–2):208–211. doi:10.1016/j.psychres.2014.11.007

    Article  CAS  PubMed  Google Scholar 

  • Cherif H, Argaw A, Cecyre B, Bouchard A, Gagnon J, Javadi P, Desgent S, Mackie K, Bouchard JF (2015) Role of GPR55 during Axon growth and target innervation(1,2,3). eNeuro 2(5). doi:10.1523/ENEURO.0011-15.2015

  • Chiang KP, Gerber AL, Sipe JC, Cravatt BF (2004) Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet 13(18):2113–2119. doi:10.1093/hmg/ddh216

    Article  CAS  PubMed  Google Scholar 

  • Chinetti G, Griglio S, Antonucci M, Torra IP, Delerive P, Majd Z, Fruchart J-C, Chapman J, Najib J, Staels B (1998) Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem 273(40):25573–25580. doi:10.1074/jbc.273.40.25573

    Article  CAS  PubMed  Google Scholar 

  • Citraro R, Russo E, Scicchitano F, van Rijn CM, Cosco D, Avagliano C, Russo R, D’Agostino G, Petrosino S, Guida F, Gatta L, van Luijtelaar G, Maione S, Di Marzo V, Calignano A, De Sarro G (2013) Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-alpha receptor activation in a genetic model of absence epilepsy. Neuropharmacology 69:115–126. doi:10.1016/j.neuropharm.2012.11.017

    Article  CAS  PubMed  Google Scholar 

  • Citraro R, Russo E, Leo A, Russo R, Avagliano C, Navarra M, Calignano A, De Sarro G (2016) Pharmacokinetic-pharmacodynamic influence of N-palmitoylethanolamine, arachidonyl-2’-chloroethylamide and WIN 55,212-2 on the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice. Eur J Pharmacol 791:523–534. doi:10.1016/j.ejphar.2016.09.029

    Article  CAS  PubMed  Google Scholar 

  • Colle R, de Larminat D, Rotenberg S, Hozer F, Hardy P, Verstuyft C, Feve B, Corruble E (2017) Pioglitazone could induce remission in major depression: a meta-analysis. Neuropsychiatr Dis Treat 13:9–16. doi:10.2147/ndt.s121149

    Article  PubMed  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384(6604):83–87

    Article  CAS  PubMed  Google Scholar 

  • Cristino L, Starowicz K, De Petrocellis L, Morishita J, Ueda N, Guglielmotti V, Di Marzo V (2008) Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain. Neuroscience 151(4):955–968. doi:10.1016/j.neuroscience.2007.11.047

    Article  CAS  PubMed  Google Scholar 

  • Cullingford T (2008) Peroxisome proliferator-activated receptor alpha and the ketogenic diet. Epilepsia 49(Suppl 8):70–72. doi:10.1111/j.1528-1167.2008.01840.x

    Article  PubMed  Google Scholar 

  • D’Agostino G, Russo R, Avagliano C, Cristiano C, Meli R, Calignano A (2012) Palmitoylethanolamide protects against the amyloid-beta25-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease. Neuropsychopharmacology 37(7):1784–1792. doi:10.1038/npp.2012.25

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Fusco M, Becchetti A, Patrignani A, Annesi G, Gambardella A, Quattrone A, Ballabio A, Wanke E, Casari G (2000) The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy. Nat Genet 26 (3):275-276. doi:10.1038/81566

    Google Scholar 

  • Deliu E, Sperow M, Console-Bram L, Carter RL, Tilley DG, Kalamarides DJ, Kirby LG, Brailoiu GC, Brailoiu E, Benamar K, Abood ME (2015) The lysophosphatidylinositol receptor GPR55 modulates pain perception in the periaqueductal Gray. Mol Pharmacol 88(2):265–272. doi:10.1124/mol.115.099333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20(5):649–688. doi:10.1210/er.20.5.649

    CAS  PubMed  Google Scholar 

  • Deutsch DG, Ueda N, Yamamoto S (2002) The fatty acid amide hydrolase (FAAH). Prostaglandins Leukot Essent Fatty Acids 66(2-3):201–210. doi:10.1054/plef.2001.0358

    Article  CAS  PubMed  Google Scholar 

  • Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258(5090):1946–1949

    Article  CAS  PubMed  Google Scholar 

  • Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W (1996) The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384(6604):39–43. doi:10.1038/384039a0

    Article  CAS  PubMed  Google Scholar 

  • Di Filippo M, Pini LA, Pelliccioli GP, Calabresi P, Sarchielli P (2008) Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis. J Neurol Neurosurg Psychiatry 79(11):1224–1229. doi:10.1136/jnnp.2007.139071

    Article  PubMed  Google Scholar 

  • Diep TA, Madsen AN, Holst B, Kristiansen MM, Wellner N, Hansen SH, Hansen HS (2011) Dietary fat decreases intestinal levels of the anorectic lipids through a fat sensor. FASEB J 25(2):765–774. doi:10.1096/fj.10-166595

    Article  CAS  PubMed  Google Scholar 

  • Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W (1992) Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68(5):879–887. 0092-8674(92)90031-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Egertova M, Simon GM, Cravatt BF, Elphick MR (2008) Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: a new perspective on N-acylethanolamines as neural signaling molecules. J Comp Neurol 506(4):604–615. doi:10.1002/cne.21568

    Article  CAS  PubMed  Google Scholar 

  • Eissa Ahmed AA, Al-Rasheed NM (2009) Antidepressant-like effects of rosiglitazone, a PPARgamma agonist, in the rat forced swim and mouse tail suspension tests. Behav Pharmacol 20(7):635–642. doi:10.1097/FBP.0b013e328331b9bf

    Article  PubMed  CAS  Google Scholar 

  • Escriva H, Langlois MC, Mendonca RL, Pierce R, Laudet V (1998) Evolution and diversification of the nuclear receptor superfamily. Ann N Y Acad Sci 839:143–146

    Article  CAS  PubMed  Google Scholar 

  • Esposito E, Impellizzeri D, Mazzon E, Paterniti I, Cuzzocrea S (2012) Neuroprotective activities of palmitoylethanolamide in an animal model of Parkinson’s disease. PloS One 7(8):e41880. doi:10.1371/journal.pone.0041880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferre P (2004) The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53(Suppl 1):S43–S50

    Article  CAS  PubMed  Google Scholar 

  • Fidaleo M, Fanelli F, Ceru MP, Moreno S (2014) Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARalpha) and its lipid ligands. Curr Med Chem 21(24):2803–2821

    Article  CAS  PubMed  Google Scholar 

  • Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425(6953):90–93

    Article  CAS  PubMed  Google Scholar 

  • Fu J, Oveisi F, Gaetani S, Lin E, Piomelli D (2005) Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology 48(8):1147–1153

    Article  CAS  PubMed  Google Scholar 

  • Galan-Rodriguez B, Suarez J, Gonzalez-Aparicio R, Bermudez-Silva FJ, Maldonado R, Robledo P, Rodriguez de Fonseca F, Fernandez-Espejo E (2009) Oleoylethanolamide exerts partial and dose-dependent neuroprotection of substantia nigra dopamine neurons. Neuropharmacology 56(3):653–664

    Article  CAS  PubMed  Google Scholar 

  • Gardner OS, Dewar BJ, Graves LM (2005) Activation of mitogen-activated protein kinases by peroxisome proliferator-activated receptor ligands: an example of nongenomic signaling. Mol Pharmacol 68(4):933–941

    Article  CAS  PubMed  Google Scholar 

  • Germain P, Staels B, Dacquet C, Spedding M, Laudet V (2006) Overview of nomenclature of nuclear receptors. Pharmacol Rev 58(4):685–704. doi:10.1124/pr.58.4.2

    Article  CAS  PubMed  Google Scholar 

  • Gervois P, Kleemann R, Pilon A, Percevault F, Koenig W, Staels B, Kooistra T (2004) Global suppression of IL-6-induced acute phase response gene expression after chronic in vivo treatment with the peroxisome proliferator-activated receptor-alpha activator fenofibrate. J Biol Chem 279(16):16154–16160. doi:10.1074/jbc.M400346200

    Article  CAS  PubMed  Google Scholar 

  • Glass CK, Ogawa S (2006) Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6(1):44–55. doi:10.1038/nri1748

    Article  CAS  PubMed  Google Scholar 

  • Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, Tarzia G, Mor M, Trezza V, Goldberg SR, Cuomo V, Piomelli D (2005) Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. PNAS 102(51):18620–18625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Aparicio R, Moratalla R (2014) Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson s disease. Neurobiol Dis 62:416–425. doi:10.1016/j.nbd.2013.10.008

    Article  CAS  PubMed  Google Scholar 

  • Graves RA, Tontonoz P, Spiegelman BM (1992) Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression. Mol Cell Biol 12(3):1202–1208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haile CN, Kosten TA (2017) The peroxisome proliferator-activated receptor alpha agonist fenofibrate attenuates alcohol self-administration in rats. Neuropharmacology 116:364–370. doi:10.1016/j.neuropharm.2017.01.007

    Article  CAS  PubMed  Google Scholar 

  • Hampson AJ, Hill WA, Zan-Phillips M, Makriyannis A, Leung E, Eglen RM, Bornheim LM (1995) Anandamide hydroxylation by brain lipoxygenase: metabolite structures and potencies at the cannabinoid receptor. Biochim Biophys Acta 1259(2):173–179

    Article  PubMed  Google Scholar 

  • Hansen HS (2010) Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Exp Neurol 224(1):48–55. doi:10.1016/j.expneurol.2010.03.022

    Article  CAS  PubMed  Google Scholar 

  • Hansen HS (2014) Role of anorectic N-acylethanolamines in intestinal physiology and satiety control with respect to dietary fat. Pharmacol Res 86:18–25. doi:10.1016/j.phrs.2014.03.006

    Article  CAS  PubMed  Google Scholar 

  • Hansen HS, Diep TA (2009) N-acylethanolamines, anandamide and food intake. Biochem Pharmacol. doi:10.1016/j.bcp.2009.04.024

    PubMed  Google Scholar 

  • Hansen HS, Moesgaard B, Hansen HH, Petersen G (2000) N-Acylethanolamines and precursor phospholipids – relation to cell injury. Chem Phys Lipids 108(1–2):135–150. S0009308400001924 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O'Banion K, Klockgether T, Van Leuven F, Landreth GE (2005) Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 128(Pt 6):1442–1453. doi:10.1093/brain/awh452

    Article  PubMed  Google Scholar 

  • Hess R, Staubli W, Riess W (1965) Nature of the hepatomegalic effect produced by ethyl-chlorophenoxy-isobutyrate in the rat. Nature 208(5013):856–858

    Article  CAS  PubMed  Google Scholar 

  • Huganir RL, Greengard P (1990) Regulation of neurotransmitter receptor desensitization by protein phosphorylation. Neuron 5(5):555–567

    Article  CAS  PubMed  Google Scholar 

  • Issemann I, Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347(6294):645–650. doi:10.1038/347645a0

    Article  CAS  PubMed  Google Scholar 

  • Jiang Q, Heneka M, Landreth GE (2008) The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer’s disease: therapeutic implications. CNS Drugs 22(1):1–14

    Article  CAS  PubMed  Google Scholar 

  • Jiang B, Wang YJ, Wang H, Song L, Huang C, Zhu Q, Wu F, Zhang W (2017) Antidepressant-like effects of fenofibrate in mice via the hippocampal brain-derived neurotrophic factor signalling pathway. Br J Pharmacol 174(2):177–194. doi:10.1111/bph.13668

    Article  CAS  PubMed  Google Scholar 

  • Jin P, HL Y, Tian L, Zhang F, Quan ZS (2015) Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress. Pharmacol Biochem Behav 133:146–154. doi:10.1016/j.pbb.2015.04.001

    Article  CAS  PubMed  Google Scholar 

  • Justinova Z, Mangieri RA, Bortolato M, Chefer SI, Mukhin AG, Clapper JR, King AR, Redhi GH, Yasar S, Piomelli D, Goldberg SR (2008) Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol Psychiatry 64(11):930–937. doi:10.1016/j.biopsych.2008.08.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Justinova Z, Panlilio LV, Moreno-Sanz G, Redhi GH, Auber A, Secci ME, Mascia P, Bandiera T, Armirotti A, Bertorelli R, Chefer SI, Barnes C, Yasar S, Piomelli D, Goldberg SR (2015) Effects of fatty acid amide hydrolase (FAAH) inhibitors in non-human primate models of nicotine reward and relapse. Neuropsychopharmacology 40(9):2185–2197. doi:10.1038/npp.2015.62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS, Abood ME (2009) Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. J Biol Chem 284(43):29817–29827. doi:10.1074/jbc.M109.050187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kemp DE, Schinagle M, Gao K, Conroy C, Ganocy SJ, Ismail-Beigi F, Calabrese JR (2014) PPAR-gamma agonism as a modulator of mood: proof-of-concept for pioglitazone in bipolar depression. CNS Drugs 28(6):571–581. doi:10.1007/s40263-014-0158-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kilaru A, Isaac G, Tamura P, Baxter D, Duncan SR, Venables BJ, Welti R, Koulen P, Chapman KD (2010) Lipid profiling reveals tissue-specific differences for ethanolamide lipids in mice lacking fatty acid amide hydrolase. Lipids 45(9):863–875. doi:10.1007/s11745-010-3457-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kozak KR, Crews BC, Morrow JD, Wang LH, Ma YH, Weinander R, Jakobsson PJ, Marnett LJ (2002) Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 277(47):44877–44885. doi:10.1074/jbc.M206788200

    Article  CAS  PubMed  Google Scholar 

  • Kucinski A, Syposs C, Wersinger S, Bencherif M, Stachowiak MK, Stachowiak EK (2012) Alpha7 neuronal nicotinic receptor agonist (TC-7020) reverses increased striatal dopamine release during acoustic PPI testing in a transgenic mouse model of schizophrenia. Schizophr Res 136(1–3):82–87

    Article  CAS  PubMed  Google Scholar 

  • Kuehl FA, Jacob TA, Ganley OH, Ormond RE, Meisinger MAP (1957) The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent. J Am Chem Soc 79(20):5577–5578. doi:10.1021/ja01577a066

    Article  CAS  Google Scholar 

  • Lambert DM, Vandevoorde S, Diependaele G, Govaerts SJ, Robert AR (2001) Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice. Epilepsia 42(3):321–327

    Article  CAS  PubMed  Google Scholar 

  • Landreth G, Jiang Q, Mandrekar S, Heneka M (2008) PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 5(3):481–489. doi:10.1016/j.nurt.2008.05.003. S1933-7213(08)00092-5 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laudet V, Hanni C, Coll J, Catzeflis F, Stehelin D (1992) Evolution of the nuclear receptor gene superfamily. EMBO J 11(3):1003–1013

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lefebvre P, Chinetti G, Fruchart JC, Staels B (2006) Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 116(3):571–580. doi:10.1172/JCI27989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373(9657):31–41. doi:10.1016/S0140-6736(08)61764-X

    Article  CAS  PubMed  Google Scholar 

  • Leung D, Saghatelian A, Simon GM, Cravatt BF (2006) Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids. Biochemistry (Mosc) 45(15):4720–4726. doi:10.1021/bi060163l

    Article  CAS  Google Scholar 

  • Lo Verme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A, Piomelli D (2005) The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 67(1):15–19. doi:10.1124/mol.104.006353

    Article  CAS  PubMed  Google Scholar 

  • Loria F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangomez M, Guaza C, Di Marzo V, Docagne F (2008) Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci 28(4):633–641. doi:10.1111/j.1460-9568.2008.06377.x

    Article  PubMed  Google Scholar 

  • Losel R, Wehling M (2003) Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol 4(1):46–56

    Article  PubMed  CAS  Google Scholar 

  • Losel RM, Falkenstein E, Feuring M, Schultz A, Tillmann HC, Rossol-Haseroth K, Wehling M (2003) Nongenomic steroid action: controversies, questions, and answers. Physiol Rev 83(3):965–1016

    Article  PubMed  Google Scholar 

  • Luchicchi A, Lecca S, Carta S, Pillolla G, Muntoni AL, Yasar S, Goldberg SR, Pistis M (2010) Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR-alpha nuclear receptors. Addict Biol 15(3):277–288. doi:10.1111/j.1369-1600.2010.00222.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandard S, Muller M, Kersten S (2004) Peroxisome proliferator-activated receptor alpha target genes. Cell Mol Life Sci 61(4):393–416. doi:10.1007/s00018-003-3216-3

    Article  CAS  PubMed  Google Scholar 

  • Mascia P, Pistis M, Justinova Z, Panlilio LV, Luchicchi A, Lecca S, Scherma M, Fratta W, Fadda P, Barnes C, Redhi GH, Yasar S, Le Foll B, Tanda G, Piomelli D, Goldberg SR (2011) Blockade of nicotine reward and reinstatement by activation of alpha-type peroxisome proliferator-activated receptors. Biol Psychiatry 69(7):633–641. doi:10.1016/j.biopsych.2010.07.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mattace Raso G, Russo R, Calignano A, Meli R (2014) Palmitoylethanolamide in CNS health and disease. Pharmacol Res 86:32–41. doi:10.1016/j.phrs.2014.05.006

    Article  CAS  PubMed  Google Scholar 

  • Mazzola C, Medalie J, Scherma M, Panlilio LV, Solinas M, Tanda G, Drago F, Cadet JL, Goldberg SR, Yasar S (2009) Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors. Learn Mem 16 (5):332-337. doi:16/5/332 [pii] 10.1101/lm.1145209

  • Melis M, Pistis M (2014) Targeting the interaction between fatty acid ethanolamides and nicotinic receptors: therapeutic perspectives. Pharmacol Res 86:42–49. doi:10.1016/j.phrs.2014.03.009

    Article  CAS  PubMed  Google Scholar 

  • Melis M, Pillolla G, Luchicchi A, Muntoni AL, Yasar S, Goldberg SR, Pistis M (2008) Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors. J Neurosci 28(51):13985–13994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melis M, Carta S, Fattore L, Tolu S, Yasar S, Goldberg SR, Fratta W, Maskos U, Pistis M (2010) Peroxisome proliferator-activated receptors-alpha modulate dopamine cell activity through nicotinic receptors. Biol Psychiatry 68(3):256–264. doi:10.1016/j.biopsych.2010.04.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melis M, Carta G, Pistis M, Banni S (2013a) Physiological role of peroxisome proliferator-activated receptors type alpha on dopamine systems. CNS Neurol Disord Drug Targets 12(1):70–77

    Article  CAS  PubMed  Google Scholar 

  • Melis M, Scheggi S, Carta G, Madeddu C, Lecca S, Luchicchi A, Cadeddu F, Frau R, Fattore L, Fadda P, Ennas MG, Castelli MP, Fratta W, Schilstrom B, Banni S, De Montis MG, Pistis M (2013b) PPARalpha regulates cholinergic-driven activity of midbrain dopamine neurons via a novel mechanism involving alpha7 nicotinic acetylcholine receptors. J Neurosci 33(14):6203–6211. doi:10.1523/JNEUROSCI.4647-12.2013

    Article  CAS  PubMed  Google Scholar 

  • Mineur YS, Picciotto MR (2010) Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends Pharmacol Sci 31(12):580–586. doi:10.1016/j.tips.2010.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moraes LA, Swales KE, Wray JA, Damazo A, Gibbins JM, Warner TD, Bishop-Bailey D (2007) Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets. Blood 109(9):3741–3744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM (2014) Activation of GPR119 by fatty acid agonists augments insulin release from clonal beta-cells and isolated pancreatic islets and improves glucose tolerance in mice. Biol Chem 395(4):453–464. doi:10.1515/hsz-2013-0255

    Article  CAS  PubMed  Google Scholar 

  • Moreno S, Farioli-Vecchioli S, Ceru MP (2004) Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123(1):131–145

    Article  CAS  PubMed  Google Scholar 

  • Morishita J, Okamoto Y, Tsuboi K, Ueno M, Sakamoto H, Maekawa N, Ueda N (2005) Regional distribution and age-dependent expression of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D in rat brain. J Neurochem 94(3):753–762. doi:10.1111/j.1471-4159.2005.03234.x

    Article  CAS  PubMed  Google Scholar 

  • Nadalin S, Giacometti J, Buretic-Tomljanovic A (2014) PPARalpha-L162V polymorphism is not associated with schizophrenia risk in a Croatian population. Prostaglandins Leukot Essent Fatty Acids 91(5):221–225. doi:10.1016/j.plefa.2014.07.003

    Article  CAS  PubMed  Google Scholar 

  • Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59(12):1151–1159

    Article  CAS  PubMed  Google Scholar 

  • Nyilas R, Dudok B, Urban GM, Mackie K, Watanabe M, Cravatt BF, Freund TF, Katona I (2008) Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals. J Neurosci 28(5):1058–1063. doi:10.1523/JNEUROSCI.5102-07.2008

    Article  CAS  PubMed  Google Scholar 

  • Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 362(4):928–934. doi:10.1016/j.bbrc.2007.08.078

    Article  CAS  PubMed  Google Scholar 

  • Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N (2004) Molecular characterization of a phospholipase D generating anandamide and its congeners. J Biol Chem 279(7):5298–5305

    Article  CAS  PubMed  Google Scholar 

  • Owen MJ, Sawa A, Mortensen PB (2016) Schizophrenia. Lancet doi:10.1016/S0140-6736(15)01121-6

    Google Scholar 

  • Panlilio LV, Justinova Z, Mascia P, Pistis M, Luchicchi A, Lecca S, Barnes C, Redhi GH, Adair J, Heishman SJ, Yasar S, Aliczki M, Haller J, Goldberg SR (2012) Novel use of a lipid-lowering fibrate medication to prevent nicotine reward and relapse: preclinical findings. Neuropsychopharmacology 37(8):1838–1847. doi:10.1038/npp.2012.31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pazos MR, Nunez E, Benito C, Tolon RM, Romero J (2004) Role of the endocannabinoid system in Alzheimer’s disease: new perspectives. Life Sci 75(16):1907–1915. doi:10.1016/j.lfs.2004.03.026. S0024-3205(04)00560-0 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Petrosino S, Iuvone T, Di Marzo V (2010) N-palmitoyl-ethanolamine: Biochemistry and new therapeutic opportunities. Biochimie 92(6):724–727. doi:10.1016/j.biochi.2010.01.006

    Article  CAS  PubMed  Google Scholar 

  • Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS (2015) Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states. Neuropharmacology 96(Pt B):235–243. doi:10.1016/j.neuropharm.2014.12.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pichat P, Bergis OE, Terranova JP, Urani A, Duarte C, Santucci V, Gueudet C, Voltz C, Steinberg R, Stemmelin J, Oury-Donat F, Avenet P, Griebel G, Scatton B (2007) SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (II) efficacy in experimental models predictive of activity against cognitive symptoms of schizophrenia. Neuropsychopharmacology 32(1):17–34. doi:10.1038/sj.npp.1301188

    Article  CAS  PubMed  Google Scholar 

  • Pietr M, Kozela E, Levy R, Rimmerman N, Lin YH, Stella N, Vogel Z, Juknat A (2009) Differential changes in GPR55 during microglial cell activation. FEBS Lett 583(12):2071–2076. doi:10.1016/j.febslet.2009.05.028

    Article  CAS  PubMed  Google Scholar 

  • Pinto M, Nissanka N, Peralta S, Brambilla R, Diaz F, Moraes CT (2016) Pioglitazone ameliorates the phenotype of a novel Parkinson’s disease mouse model by reducing neuroinflammation. Mol Neurodegener 11:25. doi:10.1186/s13024-016-0090-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Piomelli D (2013) A fatty gut feeling. Trends Endocrinol Metab 24(7):332–341. doi:10.1016/j.tem.2013.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pistis M, Melis M (2010) From surface to nuclear receptors: the endocannabinoid family extends its assets. Curr Med Chem 17(14):1450–1467

    Article  CAS  PubMed  Google Scholar 

  • Porta N, Vallee L, Lecointe C, Bouchaert E, Staels B, Bordet R, Auvin S (2009) Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, exerts anticonvulsive properties. Epilepsia 50(4):943–948. doi:10.1111/j.1528-1167.2008.01901.x

    Article  CAS  PubMed  Google Scholar 

  • Pringsheim T, Jette N, Frolkis A, Steeves TD (2014) The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 29(13):1583–1590. doi:10.1002/mds.25945

    Article  PubMed  Google Scholar 

  • Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, Scheggi S, Carta G, Murru E, Aroni S, Muntoni AL, Pistis M (2013) PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings. PloS One 8(5):e64541. doi:10.1371/journal.pone.0064541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahman IA, Tsuboi K, Uyama T, Ueda N (2014) New players in the fatty acyl ethanolamide metabolism. Pharmacol Res 86:1–10. doi:10.1016/j.phrs.2014.04.001

    Article  CAS  PubMed  Google Scholar 

  • Randy LH, Guoying B (2007) Agonism of peroxisome proliferator receptor-gamma may have therapeutic potential for neuroinflammation and Parkinson’s disease. Curr Neuropharmacol 5(1):35–46

    Article  PubMed  PubMed Central  Google Scholar 

  • Rasgon NL, Kenna HA, Williams KE, Powers B, Wroolie T, Schatzberg AF (2010) Rosiglitazone add-on in treatment of depressed patients with insulin resistance: a pilot study. Sci World J 10:321–328. doi:10.1100/tsw.2010.32

    Article  CAS  Google Scholar 

  • Reed GM, Rebello TJ, Pike KM, Medina-Mora ME, Gureje O, Zhao M, Dai Y, Roberts MC, Maruta T, Matsumoto C, Krasnov VN, Kulygina M, Lovell AM, Stona AC, Sharan P, Robles R, Gaebel W, Zielasek J, Khoury B, de Jesus Mari J, Luis Ayuso-Mateos J, Evans SC, Kogan CS, Saxena S (2015) WHO’s global clinical practice network for mental health. Lancet Psychiatry 2(5):379–380. doi:10.1016/S2215-0366(15)00183-2

    Article  PubMed  Google Scholar 

  • Reguero L, Puente N, Elezgarai I, Ramos-Uriarte A, Gerrikagoitia I, Bueno-Lopez JL, Donate F, Grandes P (2014) Subcellular localization of NAPE-PLD and DAGL-alpha in the ventromedial nucleus of the hypothalamus by a preembedding immunogold method. Histochem Cell Biol 141(5):543–550. doi:10.1007/s00418-013-1174-x

    Article  CAS  PubMed  Google Scholar 

  • Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7(3):137–152. doi:10.1038/nrneurol.2011.2

    Article  PubMed  PubMed Central  Google Scholar 

  • Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, Zvartau-Hind ME, Hosford DA, Roses AD (2006) Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 6(4):246–254. doi:10.1038/sj.tpj.6500369

    CAS  PubMed  Google Scholar 

  • Rodriguez de Fonseca F, Navarro M, Gomez R, Escuredo L, Nava F, Fu J, Murillo-Rodriguez E, Giuffrida A, LoVerme J, Gaetani S, Kathuria S, Gall C, Piomelli D (2001) An anorexic lipid mediator regulated by feeding. Nature 414(6860):209–212

    Article  CAS  PubMed  Google Scholar 

  • Rolland B, Marche K, Cottencin O, Bordet R (2012) The PPARalpha agonist fenofibrate reduces prepulse inhibition disruption in a neurodevelopmental model of Schizophrenia. Schizophr Res Treat 2012:839853. doi:10.1155/2012/839853

    Google Scholar 

  • Rolland B, Deguil J, Jardri R, Cottencin O, Thomas P, Bordet R (2013) Therapeutic prospects of PPARs in psychiatric disorders: a comprehensive review. Curr Drug Targets 14(7):724–732

    Article  CAS  PubMed  Google Scholar 

  • Ropero AB, Juan-Pico P, Rafacho A, Fuentes E, Bermudez-Silva FJ, Roche E, Quesada I, de Fonseca FR, Nadal A (2009) Rapid non-genomic regulation of Ca2+ signals and insulin secretion by PPAR alpha ligands in mouse pancreatic islets of Langerhans. J Endocrinol 200(2):127–138

    Article  CAS  PubMed  Google Scholar 

  • Rowley JW, Oler AJ, Tolley ND, Hunter BN, Low EN, Nix DA, Yost CC, Zimmerman GA, Weyrich AS (2011) Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 118(14):e101–e111. doi:10.1182/blood-2011-03-339705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russo SJ, Nestler EJ (2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci 14(9):609–625. doi:10.1038/nrn3381

    Article  CAS  PubMed  Google Scholar 

  • Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152(7):1092–1101. doi:10.1038/sj.bjp.0707460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sadaghiani MS, Javadi-Paydar M, Gharedaghi MH, Fard YY, Dehpour AR (2011) Antidepressant-like effect of pioglitazone in the forced swimming test in mice: the role of PPAR-gamma receptor and nitric oxide pathway. Behav Brain Res 224(2):336–343. doi:10.1016/j.bbr.2011.06.011

    Article  CAS  PubMed  Google Scholar 

  • Saha L, Bhandari S, Bhatia A, Banerjee D, Chakrabarti A (2014) Anti-kindling effect of bezafibrate, a peroxisome proliferator-activated receptors alpha agonist, in pentylenetetrazole induced kindling seizure model. J Epilepsy Res 4(2):45–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Salehi-Sadaghiani M, Javadi-Paydar M, Gharedaghi MH, Zandieh A, Heydarpour P, Yousefzadeh-Fard Y, Dehpour AR (2012) NMDA receptor involvement in antidepressant-like effect of pioglitazone in the forced swimming test in mice. Psychopharmacology (Berl) 223(3):345–355. doi:10.1007/s00213-012-2722-0

    Article  CAS  Google Scholar 

  • Saricicek A, Esterlis I, Maloney KH, Mineur YS, Ruf BM, Muralidharan A, Chen JI, Cosgrove KP, Kerestes R, Ghose S, Tamminga CA, Pittman B, Bois F, Tamagnan G, Seibyl J, Picciotto MR, Staley JK, Bhagwagar Z (2012) Persistent beta2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder. Am J Psychiatry 169(8):851–859. doi:10.1176/appi.ajp.2012.11101546

    Article  PubMed  PubMed Central  Google Scholar 

  • Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O’Dowd BF (1999) Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res 64(2):193–198

    Article  CAS  PubMed  Google Scholar 

  • Scheggi S, Melis M, De Felice M, Aroni S, Muntoni AL, Pelliccia T, Gambarana C, De Montis MG, Pistis M (2016) PPARalpha modulation of mesolimbic dopamine transmission rescues depression-related behaviors. Neuropharmacology 110(Pt A):251–259. doi:10.1016/j.neuropharm.2016.07.024

    Article  CAS  PubMed  Google Scholar 

  • Scherma M, Panlilio LV, Fadda P, Fattore L, Gamaleddin I, Le Foll B, Justinova Z, Mikics E, Haller J, Medalie J, Stroik J, Barnes C, Yasar S, Tanda G, Piomelli D, Fratta W, Goldberg SR (2008) Inhibition of anandamide hydrolysis by URB597 reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J Pharmacol Exp Ther. doi:10.1124/jpet.108.142224

    PubMed  PubMed Central  Google Scholar 

  • Scherma M, Muntoni AL, Melis M, Fattore L, Fadda P, Fratta W, Pistis M (2016) Interactions between the endocannabinoid and nicotinic cholinergic systems: preclinical evidence and therapeutic perspectives. Psychopharmacology (Berl). doi:10.1007/s00213-015-4196-3

    PubMed Central  Google Scholar 

  • Schintu N, Frau L, Ibba M, Caboni P, Garau A, Carboni E, Carta AR (2009) PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson’s disease. Eur J Neurosci 29(5):954–963

    Article  PubMed  Google Scholar 

  • Schmid HH, Schmid PC, Natarajan V (1990) N-acylated glycerophospholipids and their derivatives. Prog Lipid Res 29(1):1–43

    Article  CAS  PubMed  Google Scholar 

  • Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA (1992) Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol 6(10):1634–1641

    CAS  PubMed  Google Scholar 

  • Scuderi C, Steardo L (2013) Neuroglial roots of neurodegenerative diseases: therapeutic potential of palmitoylethanolamide in models of Alzheimer’s disease. CNS Neurol Disord Drug Targets 12(1):62–69

    Article  CAS  PubMed  Google Scholar 

  • Scuderi C, Esposito G, Blasio A, Valenza M, Arietti P, Steardo L, Jr., Carnuccio R, De Filippis D, Petrosino S, Iuvone T, Di Marzo V, Steardo L (2011) Palmitoylethanolamide counteracts reactive astrogliosis induced by beta-amyloid peptide. J Cell Mol Med 15 (12):2664-2674. doi:10.1111/j.1582-4934.2011.01267.x

  • Scuderi C, Valenza M, Stecca C, Esposito G, Carratu MR, Steardo L (2012) Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-alpha. J Neuroinflamm 9:49. doi:10.1186/1742-2094-9-21

    Article  CAS  Google Scholar 

  • Sepanjnia K, Modabbernia A, Ashrafi M, Modabbernia MJ, Akhondzadeh S (2012) Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: randomized double-blind placebo-controlled trial. Neuropsychopharmacology 37(9):2093–2100. doi:10.1038/npp.2012.58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheerin AH, Zhang X, Saucier DM, Corcoran ME (2004) Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid. Epilepsia 45(10):1184–1188. doi:10.1111/j.0013-9580.2004.16604.x

    Article  CAS  PubMed  Google Scholar 

  • Sher T, Yi HF, McBride OW, Gonzalez FJ (1993) cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry (Mosc) 32(21):5598–5604

    Article  CAS  Google Scholar 

  • Sheu MY, Fowler AJ, Kao J, Schmuth M, Schoonjans K, Auwerx J, Fluhr JW, Man MQ, Elias PM, Feingold KR (2002) Topical peroxisome proliferator activated receptor-alpha activators reduce inflammation in irritant and allergic contact dermatitis models. J Invest Dermatol 118(1):94–101. doi:10.1046/j.0022-202x.2001.01626.x

    Article  CAS  PubMed  Google Scholar 

  • Shohami E, Mechoulam R (2006) Multiple sclerosis may disrupt endocannabinoid brain protection mechanism. Proc Natl Acad Sci U S A 103(16):6087–6088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon GM, Cravatt BF (2010) Characterization of mice lacking candidate N-acyl ethanolamine biosynthetic enzymes provides evidence for multiple pathways that contribute to endocannabinoid production in vivo. Mol Biosyst 6(8):1411–1418. doi:10.1039/c000237b

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF (2002) A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci U S A 99(12):8394–8399. doi:10.1073/pnas.08223579999/12/8394. [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Staton PC, Hatcher JP, Walker DJ, Morrison AD, Shapland EM, Hughes JP, Chong E, Mander PK, Green PJ, Billinton A, Fulleylove M, Lancaster HC, Smith JC, Bailey LT, Wise A, Brown AJ, Richardson JC, Chessell IP (2008) The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 139(1):225–236. doi:10.1016/j.pain.2008.04.006

    Article  CAS  PubMed  Google Scholar 

  • Steinlein OK (2004) Genetic mechanisms that underlie epilepsy. Nat Rev Neurosci 5 (5):400-408. doi:10.1038/nrn1388 nrn1388 [pii]

    Google Scholar 

  • Steinlein OK, Magnusson A, Stoodt J, Bertrand S, Weiland S, Berkovic SF, Nakken KO, Propping P, Bertrand D (1997) An insertion mutation of the CHRNA4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy. Hum Mol Genet 6(6):943–947

    CAS  PubMed  Google Scholar 

  • Straus DS, Glass CK (2007) Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol 28(12):551–558. doi:10.1016/j.it.2007.09.003

    Article  CAS  PubMed  Google Scholar 

  • Suarez J, Bermudez-Silva FJ, Mackie K, Ledent C, Zimmer A, Cravatt BF, de Fonseca FR (2008) Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related nuclei. J Comp Neurol 509(4):400–421. doi:10.1002/cne.21774

    Article  CAS  PubMed  Google Scholar 

  • Sutor B, Zolles G (2001) Neuronal nicotinic acetylcholine receptors and autosomal dominant nocturnal frontal lobe epilepsy: a critical review. Pflugers Arch 442(5):642–651

    Article  CAS  PubMed  Google Scholar 

  • Terrazzino S, Berto F, Dalle Carbonare M, Fabris M, Guiotto A, Bernardini D, Leon A (2004) Stearoylethanolamide exerts anorexic effects in mice via down-regulation of liver stearoyl-coenzyme A desaturase-1 mRNA expression. FASEB J 18(13):1580–1582. doi:10.1096/fj.03-1080fje

    CAS  PubMed  Google Scholar 

  • Thomsen MS, Hansen HH, Timmerman DB, Mikkelsen JD (2012) Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. Curr Pharm Des 16(3):323–343

    Article  Google Scholar 

  • Thorp JM, Waring WS (1962) Modification of metabolism and distribution of lipids by ethyl chlorophenoxyisobutyrate. Nature 194:948–949

    Article  CAS  PubMed  Google Scholar 

  • Thurman DJ, Beghi E, Begley CE, Berg AT, Buchhalter JR, Ding D, Hesdorffer DC, Hauser WA, Kazis L, Kobau R, Kroner B, Labiner D, Liow K, Logroscino G, Medina MT, Newton CR, Parko K, Paschal A, Preux PM, Sander JW, Selassie A, Theodore W, Tomson T, Wiebe S (2011) Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia 52(Suppl 7):2–26. doi:10.1111/j.1528-1167.2011.03121.x

    Article  CAS  PubMed  Google Scholar 

  • Tizabi Y, Rezvani AH, Russell LT, Tyler KY, Overstreet DH (2000) Depressive characteristics of FSL rats: involvement of central nicotinic receptors. Pharmacol Biochem Behav 66(1):73–77

    Article  CAS  PubMed  Google Scholar 

  • Tsuboi K, Sun YX, Okamoto Y, Araki N, Tonai T, Ueda N (2005) Molecular characterization of N-acylethanolamine-hydrolyzing acid amidase, a novel member of the choloylglycine hydrolase family with structural and functional similarity to acid ceramidase. J Biol Chem 280(12):11082–11092. doi:10.1074/jbc.M413473200

    Article  CAS  PubMed  Google Scholar 

  • Tsuboi K, Takezaki N, Ueda N (2007a) The N-acylethanolamine-hydrolyzing acid amidase (NAAA). Chem Biodivers 4(8):1914–1925. doi:10.1002/cbdv.200790159

    Article  CAS  PubMed  Google Scholar 

  • Tsuboi K, Zhao LY, Okamoto Y, Araki N, Ueno M, Sakamoto H, Ueda N (2007b) Predominant expression of lysosomal N-acylethanolamine-hydrolyzing acid amidase in macrophages revealed by immunochemical studies. Biochim Biophys Acta 1771(5):623–632. doi:10.1016/j.bbalip.2007.03.005

    Article  CAS  PubMed  Google Scholar 

  • Tsuboi K, Okamoto Y, Ikematsu N, Inoue M, Shimizu Y, Uyama T, Wang J, Deutsch DG, Burns MP, Ulloa NM, Tokumura A, Ueda N (2011) Enzymatic formation of N-acylethanolamines from N-acylethanolamine plasmalogen through N-acylphosphatidylethanolamine-hydrolyzing phospholipase D-dependent and -independent pathways. Biochim Biophys Acta 1811(10):565–577. doi:10.1016/j.bbalip.2011.07.009

    Article  CAS  PubMed  Google Scholar 

  • Tyndale RF, Payne JI, Gerber AL, Sipe JC (2007) The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: studies of drug use and dependence in Caucasians. Am J Med Genet B Neuropsychiatr Genet 144B(5):660–666. doi:10.1002/ajmg.b.30491

    Article  CAS  PubMed  Google Scholar 

  • Ueda N, Yamamoto K, Yamamoto S, Tokunaga T, Shirakawa E, Shinkai H, Ogawa M, Sato T, Kudo I, Inoue K et al (1995) Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid receptor agonist. Biochim Biophys Acta 1254(2):127–134

    Article  PubMed  Google Scholar 

  • Ueda N, Liu Q, Yamanaka K (2001) Marked activation of the N-acylphosphatidylethanolamine-hydrolyzing phosphodiesterase by divalent cations. Biochim Biophys Acta 1532(1-2):121–127

    Article  CAS  PubMed  Google Scholar 

  • Ueda N, Tsuboi K, Uyama T (2010a) Enzymological studies on the biosynthesis of N-acylethanolamines. Biochim Biophys Acta (BBA) – Mol Cell Biol Lipids 1801(12):1274–1285. doi:10.1016/j.bbalip.2010.08.010

    Article  CAS  Google Scholar 

  • Ueda N, Tsuboi K, Uyama T (2010b) N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA). Prog Lipid Res 49(4):299–315. doi:10.1016/j.plipres.2010.02.003

    Article  CAS  PubMed  Google Scholar 

  • Umathe SN, Manna SS, Jain NS (2011) Involvement of endocannabinoids in antidepressant and anti-compulsive effect of fluoxetine in mice. Behav Brain Res 223(1):125–134. doi:10.1016/j.bbr.2011.04.031

    Article  CAS  PubMed  Google Scholar 

  • Varvel NH, Jiang J, Dingledine R (2015) Candidate drug targets for prevention or modification of epilepsy. Annu Rev Pharmacol Toxicol 55:229–247. doi:10.1146/annurev-pharmtox-010814-124607

    Article  CAS  PubMed  Google Scholar 

  • Volkow ND, Koob GF, McLellan AT (2016) Neurobiologic advances from the brain disease model of addiction. N Engl J Med 374(4):363–371. doi:10.1056/NEJMra1511480

    Article  CAS  PubMed  Google Scholar 

  • Wangensteen T, Akselsen H, Holmen J, Undlien D, Retterstøl L (2010) A common haplotype in NAPEPLD is associated with severe obesity in a norwegian population-based cohort (the HUNT study). Obesity 19(3):612–617. doi:10.1038/oby.2010.219

    Article  PubMed  CAS  Google Scholar 

  • Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S (2005) Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry 13(11):950–958. doi:10.1176/appi.ajgp.13.11.950

    PubMed  Google Scholar 

  • Whiteford HA, Ferrari AJ, Baxter AJ, Charlson FJ, Degenhardt L (2013) How did we arrive at burden of disease estimates for mental and illicit drug use disorders in the Global Burden of Disease Study 2010? Curr Opin Psychiatry 26(4):376–383. doi:10.1097/YCO.0b013e328361e60f

    Article  PubMed  Google Scholar 

  • World Health Organization (2003) Investing in mental health

    Google Scholar 

  • Xu J, Xiao G, Trujillo C, Chang V, Blanco L, Joseph SB, Bassilian S, Saad MF, Tontonoz P, Lee WN, Kurland IJ (2002) Peroxisome proliferator-activated receptor alpha (PPARalpha) influences substrate utilization for hepatic glucose production. J Biol Chem 277(52):50237–50244. doi:10.1074/jbc.M201208200

    Article  CAS  PubMed  Google Scholar 

  • Yang R, Wang P, Chen Z, Hu W, Gong Y, Zhang W, Huang C (2017) WY-14643, a selective agonist of peroxisome proliferator-activated receptor-alpha, ameliorates lipopolysaccharide-induced depressive-like behaviors by preventing neuroinflammation and oxido-nitrosative stress in mice. Pharmacol Biochem Behav 153:97–104. doi:10.1016/j.pbb.2016.12.010

    Article  CAS  PubMed  Google Scholar 

  • Yu M, Ives D, Ramesha CS (1997) Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. J Biol Chem 272(34):21181–21186

    Article  CAS  PubMed  Google Scholar 

  • Yu HL, Deng XQ, Li YJ, Li YC, Quan ZS, Sun XY (2011) N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice. Pharmacol Rep 63(3):834–839

    Article  CAS  PubMed  Google Scholar 

  • Yu HL, Sun LP, Li MM, Quan ZS (2015) Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair. Neurosci Lett 593:24–28. doi:10.1016/j.neulet.2015.03.019

    Article  CAS  PubMed  Google Scholar 

  • Zanaletti R, Bettinetti L, Castaldo C, Cocconcelli G, Comery T, Dunlop J, Gaviraghi G, Ghiron C, Haydar SN, Jow F, Maccari L, Micco I, Nencini A, Scali C, Turlizzi E, Valacchi M (2012) Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (SEN15924, WAY-361789). J Med Chem 55(10):4806–4823

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042, Cagliari, Italy

    Marco Pistis

  2. Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Cagliari, Italy

    Marco Pistis & Anna Lisa Muntoni

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  1. Marco Pistis
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  2. Anna Lisa Muntoni
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Correspondence to Marco Pistis .

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  1. Dept Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy

    Miriam Melis

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Pistis, M., Muntoni, A.L. (2017). Roles of N-Acylethanolamines in Brain Functions and Neuropsychiatric Diseases. In: Melis, M. (eds) Endocannabinoids and Lipid Mediators in Brain Functions. Springer, Cham. https://doi.org/10.1007/978-3-319-57371-7_11

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