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Modulation of Serotonin Firing Activity Through CB1 Agonists and FAAH Inhibitors

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Endocannabinoid Regulation of Monoamines in Psychiatric and Neurological Disorders

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Abstract

The psychological feelings produced by cannabis have been described as fatuous euphoria, elation, and talkativeness. Alternatively, cannabis can induce low mood and depression especially after chronic use. Despite these clinical evidences, little was known about the capacity of cannabis to modulate serotonin (5-Hydroxytryptamine, 5-HT), the main neurotransmitter implicated in the regulation of mood and the pathology of mood disorders.

In the past 10 years, our laboratory has attempted to clarify how the cannabinoid type 1 receptor (CB1R) agonists, antagonists, and the fatty acid amide hydrolase (FAAH) inhibitors modulate the firing activity of 5-HT neurons located in the dorsal raphe nucleus.

While the CB1R agonist R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolol[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) produces a bell-shaped curve, increasing 5-HT firing at low doses (0.1–0.3 mg/kg) and decreasing firing at higher doses (>0.3 mg/kg), the FAAH inhibitor [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate (URB597) produces a sigma-shaped curve, with a plateau at the highest doses tested (0.3 mg/kg). Δ9-Tetrahydrocannabinol (THC) produces a mixed response on 5-HT firing activity with 26 % of neurons showing an increase, 33 % showing a decrease, and 42 % showing no response. However, after 4 days, intraperitoneal (i.p.) injections of THC (1 mg/kg) produced a significant elevation of firing. The increase in firing following WIN 55,212-2 and THC was prevented by the CB1R antagonist rimonabant. Finally, both WIN 55,212-2 and THC evoked a robust decrease in 5-HT firing after long-term administration in adolescence.

These data show that CB1R agonists and FAAH inhibitors interact with the 5-HT system and that this effect may be related to emotional behaviors.

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References

  • Adamec R, Creamer K, Bartoszyk GD, Burton P (2004) Prophylactic and therapeutic effects of acute systemic injections of EMD 281014, a selective serotonin 2A receptor antagonist on anxiety induced by predator stress in rats. Eur J Pharmacol 504:79–96

    Article  PubMed  CAS  Google Scholar 

  • Aghajanian GK, Foote WE, Sheard MH (1968) Lysergic acid diethylamide: sensitive neuronal units in the midbrain raphe. Science 161:706–708

    Article  PubMed  CAS  Google Scholar 

  • Allers K, Sharp T (2003) Neurochemical and anatomical identification of fast- and slow -firing neurones in the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo. Neuroscience 122:193–204

    Article  PubMed  CAS  Google Scholar 

  • Artigas F (1993) 5-HT and Antidepressants: new views from Microdialysis Studies. Trends Pharmacol Sci 14:262

    Article  PubMed  CAS  Google Scholar 

  • Artigas F, Romero L, Montigny C de, Blier P (1996) Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci 19:378–383

    Article  PubMed  CAS  Google Scholar 

  • Aso E, Ozaita A, Valdizan EM, Ledent C, Pazos A, Maldonado R, Valverde O (2008) BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J Neurochem 105:565–572

    Article  PubMed  CAS  Google Scholar 

  • Bambico FR, Gobbi G (2008) The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert Opin Ther Targets 12:1347–1366

    Article  PubMed  CAS  Google Scholar 

  • Bambico FR, Katz N, Debonnel G, Gobbi G (2007) Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J Neurosci 27:11700–11711

    Article  PubMed  CAS  Google Scholar 

  • Bambico FR, Duranti A, Tontini A, Tarzia G, Gobbi G (2009) Endocannabinoids in the treatment of mood disorders: evidence from animal models. Current Pharm Des 15:1623–1646

    Article  CAS  Google Scholar 

  • Bambico FR, Cassano T, Dominguez-Lopez S, Katz N, Walker CD, Piomelli D, Gobbi G (2010a) Genetic deletion of fatty acid amide hydrolase alters emotional behavior and serotonergic transmission in the dorsal raphe, prefrontal cortex, and hippocampus. Neuropsychopharmacol 35:2083–2100

    Article  CAS  Google Scholar 

  • Bambico FR, Nguyen NT, Katz N, Gobbi G (2010b) Chronic exposure during adolescence but not during adulthood impairs emotional behaviour and monoaminergic transmission. Neurobiol Dis 37:641–655

    Article  CAS  Google Scholar 

  • Bambico FR, Hattan PR, Garant JP, Gobbi G (2012) Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission. Progress Neuro-Psychoph 38:88–96

    Article  CAS  Google Scholar 

  • Banerjee SP, Snyder SH, Mechoulam R (1975) Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes. J Pharmacol Exp Ther 194:74–81

    PubMed  CAS  Google Scholar 

  • Barann M, Molderings G, Bruss M, Bonisch H, Urban BW, Gothert M (2002) Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site. British J Pharmacol 137:589–596

    Article  CAS  Google Scholar 

  • Belue RC, Howlett AC, Westlake TM, Hutchings DE (1995) The ontogeny of cannabinoid receptors in the brain of postnatal and aging rats. Neurotoxicol Teratol 17:25–30

    Article  PubMed  CAS  Google Scholar 

  • Besson A, Haddjeri N, Blier P, Montigny C de (2000) Effects of the co-administration of mirtazapine and paroxetine on serotonergic neurotransmission in the rat brain. European Neuropsychopharm 10:177–188

    Article  CAS  Google Scholar 

  • Beyer CE, Dwyer JM, Piesla MJ, Platt BJ, Shen R, Rahman Z, Chan K, Manners MT, Samad TA, Kennedy JD, Bingham B, Whiteside GT (2010) Depression-like phenotype following chronic CB1 receptor antagonism. Neurobiol Dis 39:148–155

    Article  PubMed  CAS  Google Scholar 

  • Biscaia M, Marin S, Fernandez B, Marco EM, Rubio M, Guaza C, Ambrosio E, Viveros MP (2003) Chronic treatment with CP 55,940 during the peri-adolescent period differentially affects the behavioural responses of male and female rats in adulthood. Psychopharmacol 170:301–308

    Article  CAS  Google Scholar 

  • Blier P, Montigny C de (1994) Current Advances and Trends in the Treatment of Depression. Trends Pharmacol Sci 15:220–226

    Article  PubMed  CAS  Google Scholar 

  • Buchanan CM, Eccles JS, Becker JB (1992) Are adolescents the victims of ragin hormones—evidence for activational effects of hormones on moods and behavior at adolescence. Psychol Bull 111:62–107

    Article  PubMed  CAS  Google Scholar 

  • Calizo LH, Akanwa A, Ma X, Pan Y, Lemos JC, Craige C, Heemstra LA, Beck SG (2011) Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence. Neuropharmacol 61:524–543

    Article  CAS  Google Scholar 

  • Castagne V, Moser P, Roux S, Porsolt RD (2011) Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Current protocols in neuroscience/ editorial board, Jacqueline N Crawley [et al] Chapter 8:Unit 8 10A

    Google Scholar 

  • CPHA (2012) CPS: Compendium of Pharmaceuticals and Specialties. Canadian Pharmacists Assoc, Canada

    Google Scholar 

  • Darmani NA (2001) Cannabinoids of diverse structure inhibit two DOI-induced 5-HT(2A) receptor-mediated behaviors in mice. Pharmacol Biochem Be 68:311–317

    Article  CAS  Google Scholar 

  • Deakin JF (1988) 5HT2 receptors, depression and anxiety. Pharmacol Biochem Be 29:819–820

    Article  CAS  Google Scholar 

  • Deas D (2006) Adolescent substance abuse and psychiatric comorbidities. J Clin Psych 67(Suppl 7):18–23

    Google Scholar 

  • Descarries L, Watkins K, Garcia S, Beaudet A (1982) The serotonin neurons in nucleus raphe dorsalis of adult rat: a light and electron microscope radioautographic study. J Comp Neurol 207:239–254

    Article  PubMed  CAS  Google Scholar 

  • Devlin MG, Christopoulos A (2002) Modulation of cannabinoid agonist binding by 5-HT in the rat cerebellum. J Neurochem 80:1095–1102

    Article  PubMed  CAS  Google Scholar 

  • Domànguez-López S, Mahar I, Bambico FR, Labonté B, Ochoa-Sánchez R, Leyton M, Gobbi G (2011) Short term effects of melatonin and pinealectomy on serotoner-gic neuronal activity across the light-dark cycle. J Psychopharmacol 26(6):830–844

    Article  Google Scholar 

  • Earleywine M (2005) Understanding Marijuana: A New Look at the Scientific Evidence. Oxford Univ. Press, USA

    Google Scholar 

  • Egashira N, Matsuda T, Koushi E, Higashihara F, Mishima K, Chidori S, Hasebe N, Iwasaki K, Nishimura R, Oishi R, Fujiwara M (2008) Delta(9)-tetrahydrocannabinol prolongs the immobility time in the mouse forced swim test: involvement of cannabinoid CB(1) receptor and serotonergic system. Eur J Pharmacol 589(1–3):117–121

    Article  PubMed  CAS  Google Scholar 

  • Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience 119:481–496

    Article  PubMed  CAS  Google Scholar 

  • El-Alfy AT, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, Khan I, ElSohly M, Ross S (2010) Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Be 95:434–442

    Article  CAS  Google Scholar 

  • Elbatsh M, Moklas M, Marsden C, Kendall D (2012) Antidepressant-like effects of Δ9-tetrahydrocannabinol and rimonabant in the olfactory bulbectomised rat model of depression Pharm Bioch Behaviour 102:357–365

    Google Scholar 

  • Ellgren M, Artmann A, Tkalych O, Gupta A, Hansen HS, Hansen SH, Devi LA, Hurd YL (2008) Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol 18:826–834

    Article  PubMed  CAS  Google Scholar 

  • Fan P (1995) Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons. J Neurophysiol 73:907–910

    PubMed  CAS  Google Scholar 

  • Freedman J, Aghajanian G (1984) Idazoxan (RX 781094) Selectively antagonizes alpha 2-adrenoceptors on rat central neurons. Eur J Pharmacol 105:265–272

    Article  PubMed  CAS  Google Scholar 

  • Gartside S, Hajos-Korcsok E, Bagdy E, Harsing L, Sharp T, Hajos M (2000) Neurochemical and electrophysiological studies on the functional significance of burst firing in serotonergic neurons. Neurosci 98:295–300

    Article  CAS  Google Scholar 

  • Germine M, Goddard AW, Sholomskas DE, Woods SW, Charney DS, Heninger GR (1994) Response to meta-chlorophenylpiperazine in panic disorder patients and healthy subjects: influence of reduction in intravenous dosage. Psychiatry Res 54:115–133

    Article  PubMed  CAS  Google Scholar 

  • Giedd JN (2004) Structural magnetic resonance imaging of the adolescent brain. Ann N Y Acad Sci 1021:77–85

    Article  PubMed  Google Scholar 

  • Gobbi G, Blier P (2005) Effect of neurokinin-1 receptor antagonists on serotoninergic, noradrenergic and hippocampal neurons: comparison with antidepressant drugs. Peptides 26:1383–1393

    Article  PubMed  CAS  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 102:18620–18625

    Article  PubMed  CAS  Google Scholar 

  • Gobbi G, Cassano T, Radja F, Morgese MG, Cuomo V, Santarelli L, Hen R, Blier P (2007) Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function. European neuropsychopharmacol 17:328–338

    Article  CAS  Google Scholar 

  • Griebel G, Rodgers RJ, Perrault G, Sanger DJ (1997) Risk assessment behaviour: evaluation of utility in the study of 5-HT-related drugs in the rat elevated plus-maze test. Pharmacol Biochem Be 57:817–827

    Article  CAS  Google Scholar 

  • Haddjeri N, Blier P, Montigny C de (1997) Effects of long-term treatment with the alpha 2-adrenoceptor antagonist mirtazapine on 5-HT neurotransmission. Naunyn Schmiedebergs Arch Pharmacol 355:20–29

    Article  PubMed  CAS  Google Scholar 

  • Haddjeri N, Blier P, Montigny C de (1998) Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. J Neurosci 18:10150–10156

    PubMed  CAS  Google Scholar 

  • Haddjeri N, Lavoie N, Blier P (2004) Electrophysiological evidence for the tonic activation of 5-HT1A autoreceptors in the rat dorsal raphe nucleus. Neuropsychopharmacology 29:1800–1806

    Article  PubMed  CAS  Google Scholar 

  • Haigler HJ, Aghajanian GK (1974) Lysergic acid diethylamide and serotonin: a comparision of effects on serotonergic neurons and neurons receiving a serotonergic input. J Pharmacol Exp Ther 188:688–699

    PubMed  CAS  Google Scholar 

  • Haj-Dahmane S, Shen RY (2005) The wake-promoting peptide orexin-B inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling. J Neurosci 25:896–905

    Article  PubMed  CAS  Google Scholar 

  • Hajos M, Hajos-Korcsok E, Sharp T (1999) Role of the medial prefrontal cortex in 5-HT1A receptor-induced inhibition of 5-HT neuronal activity in the rat. British J Pharmacol 126:1741–1750

    Article  CAS  Google Scholar 

  • Hajos M, Allers K, Jennings K, Sharp T, Charette G, Sik A, Kocsis B (2007) Neurochemical identification of stereotypic burst-firing neurons in the rat dorsal raphe nucleus using juxtacellular labelling methods. Eur J Neurosci 25:119–126

    Article  PubMed  Google Scholar 

  • Harkany T, Keimpema E, Barabas K, Mulder J (2008) Endocannabinoid functions controlling neuronal specification during brain development. Mol Cell Endocrinol 286:84–90

    Article  Google Scholar 

  • Hayatbakhsh MR, Najman JM, Jamrozik K, Mamun AA, Alati R, Bor W (2007) Cannabis and anxiety and depression in young adults: a large prospective study. J Am Acad Child Adolesc Psychiatry 46:408–417

    Article  PubMed  Google Scholar 

  • Hermann H, Marsicano G, Lutz B (2002) Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 109:451–460

    Article  PubMed  CAS  Google Scholar 

  • Hill MN, Gorzalka BB (2005) Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Eur Neuropsychopharmacol 15:593–599

    Article  PubMed  CAS  Google Scholar 

  • Hill MN, Sun JC, Tse MT, Gorzalka BB (2006) Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment. Int J Neuropsychopharmacol 9:277–286

    Article  PubMed  CAS  Google Scholar 

  • Hill MN, Hillard CJ, Bambico FR, Patel S, Gorzalka BB, Gobbi G (2009) The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends Pharmacol Sci 30:484–493

    Article  PubMed  CAS  Google Scholar 

  • Hollander E, DeCaria C, Gully R, Nitescu A, Suckow RF, Gorman JM, Klein DF, Liebowitz MR (1991) Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder. Psychiatry research 36:1–17

    Article  PubMed  CAS  Google Scholar 

  • Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 47(Suppl 1):345–358

    Article  PubMed  CAS  Google Scholar 

  • Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA (2001) Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiat 58:322–328

    Article  PubMed  CAS  Google Scholar 

  • Iversen L (2003) Cannabis and the brain. Brain 126:1252–1270

    Article  PubMed  Google Scholar 

  • Jankowski MP, Sesack SR (2004) Prefrontal cortical projections to the rat dorsal raphe nucleus: ultrastructural features and associations with serotonin and gamma-aminobutyric acid neurons. J Comp Neurol 468:518–529

    Article  PubMed  CAS  Google Scholar 

  • Johnson KM, Ho BT, Dewey WL (1976) Effects of delta9-tetrahydrocannabinol on neurotransmitter accumulation and release mechanisms in rat forebrain synaptosomes. Life Sci 19:347–356

    Article  PubMed  CAS  Google Scholar 

  • Kimura T, Ohta T, Watanabe K, Yoshimura H, Yamamoto I (1998) Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor. Biol Pharm Bull 21:224–226

    Article  PubMed  CAS  Google Scholar 

  • Laaris N, Good CH, Lupica CR (2010) Delta9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus. Neuropharmacology 59:121–127

    Article  PubMed  CAS  Google Scholar 

  • Malone DT, Taylor DA (2001) Involvement of somatodendritic 5-HT(1A) receptors in Delta(9)-tetrahydrocannabinol-induced hypothermia in the rat. Pharmacol Biochem Be 69:595–601

    Article  CAS  Google Scholar 

  • Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003) Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology 28:402–412

    Article  PubMed  CAS  Google Scholar 

  • Martin M, Ledent C, Parmentier M, Maldonado R, Valverde O (2002) Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology 159:379–387

    Article  PubMed  CAS  Google Scholar 

  • Matsuda LA, Bonner TI, Lolait SJ (1993) Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol 327:535–550

    Article  PubMed  CAS  Google Scholar 

  • Mendiguren A, Pineda J (2009) Effect of the CB(1) receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices. British J Pharmacol 158:1579–1587

    Article  CAS  Google Scholar 

  • Mitchell PB, Morris MJ (2007) Depression and anxiety with rimonabant. Lancet 370:1671–1672

    Article  PubMed  Google Scholar 

  • Moldrich G, Wenger T (2000) Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 21:1735–1742

    Article  PubMed  CAS  Google Scholar 

  • Morales M, Wang SD, Diaz-Ruiz O, Jho DH (2004) Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon. J Comp Neurol 468:205–216

    Article  PubMed  CAS  Google Scholar 

  • Moreira FA, Grieb M, Lutz B (2004) Role of serotonin on the antidepressant-like effect induced by delta-9-tetrahydrocannabinol, but not by rimonabant. In: 18th Symposium of the International Cannabinoid Research Society Avemore, Scotland

    Google Scholar 

  • Nakazi M, Bauer U, Nickel T, Kathmann M, Schlicker E (2000) Inhibition of serotonin release in the mouse brain via presynaptic cannabinoid CB1 receptors. Naunyn Schmiedebergs Arch Pharmacol 361:19–24

    Article  PubMed  CAS  Google Scholar 

  • O’Shea M, Singh ME, McGregor IS, Mallet PE (2004) Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol 18:502–508

    Article  PubMed  Google Scholar 

  • O’Shea M, McGregor IS, Mallet PE (2006) Repeated cannabinoid exposure during perinatal, adolescent or early adult ages produces similar longlasting deficits in object recognition and reduced social interaction in rats. J Psychopharmacol 20:611–621

    Article  PubMed  Google Scholar 

  • Page ME, Brown K, Lucki I (2003) Simultaneous analyses of the neurochemical and behavioral effects of the norepinephrine reuptake inhibitor reboxetine in a rat model of antidepressant action. Psychopharmacol 165:194–201

    CAS  Google Scholar 

  • Palazzo E, Novellis V de, Petrosino S, Marabese I, Vita D, Giordano C, Di Marzo V, Mangoni GS, Rossi F, Maione S (2006) Neuropathic pain and the endocannabinoid system in the dorsal raphe: pharmacological treatment and interactions with the serotonergic system. Eur J Neurosci 24:2011–2020

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier, Amsterdam

    Google Scholar 

  • Quested DJ, Sargent PA, Cowen PJ (1997) SSRI treatment decreases prolactin and hyperthermic responses to mCPP. Psychopharmacol 133:305–308

    Article  CAS  Google Scholar 

  • Rodriguez-Gaztelumendi A, Rojo ML, Pazos A, Diaz A (2009) Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine. J Neurochem 108:1423–1433

    Article  PubMed  CAS  Google Scholar 

  • Rubino T, Vigano D, Realini N, Guidali C, Braida D, Capurro V, Castiglioni C, Cherubino F, Romualdi P, Candeletti S, Sala M, Parolaro D (2008) Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacol 33:2760–2771

    Article  CAS  Google Scholar 

  • Schneider M (2008) Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure. Addict Biol 13:253–263

    Article  PubMed  Google Scholar 

  • Spear LP (2000) Neurobehavioral changes in adolescence. Curr Dir Psychol Sci 9:111–114

    Article  Google Scholar 

  • Sprouse J, Aghajanian G (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9

    Article  PubMed  CAS  Google Scholar 

  • Szabo ST, Blier P (2001) Effects of the selective norepinephrine reuptake inhibitor reboxetine on norepinephrine and serotonin transmission in the rat hippocampus. Neuropsychopharmacol 25:845–857

    Article  CAS  Google Scholar 

  • Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83:393–411

    Article  PubMed  CAS  Google Scholar 

  • Valverde O, Torrens M (2012) CB1 receptor-deficient mice as a model for depression. Neuroscience 204:193–206

    Article  PubMed  CAS  Google Scholar 

  • Wittchen HU, Frohlich C, Behrendt S, Gunther A, Rehm J, Zimmermann P, Lieb R, Perkonigg A (2007) Cannabis use and cannabis use disorders and their relationship to mental disorders: a 10-year prospective-longitudinal community study in adolescents. Drug Alcohol Depen 88(Suppl 1):60–70

    Article  Google Scholar 

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  1. Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Av des Pins Ouest (room 220), H3A1A1, QC, Montreal, Canada

    Gabriella Gobbi MD, PhD

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    Elisabeth J. Van Bockstaele

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Gobbi, G. (2013). Modulation of Serotonin Firing Activity Through CB1 Agonists and FAAH Inhibitors. In: Van Bockstaele, E. (eds) Endocannabinoid Regulation of Monoamines in Psychiatric and Neurological Disorders. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7940-6_12

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