Selective inhibition of intestinal 5-HT improves neurobehavioral abnormalities caused by high-fat diet mice

  • Qi Pan
  • Qiongzhen Liu
  • Renling Wan
  • Praveen Kumar Kalavagunta
  • Li Liu
  • Wenting Lv
  • Tong Qiao
  • Jing ShangEmail author
  • Huali WuEmail author
Original Article


Recent literature reported the adverse effects of high-fat diet (HFD) on animal’s emotional and cognitive function. An HFD-induced obesity/hyperlipidemia is accompanied by hormonal and neurochemical changes that can lead to depression. The important roles of gut-derived serotonin (5-Hydroxytryptamine, 5-HT) during this processing have been increasingly focused. Hence, to determine the potential role of gut-derived serotonin, HFD model was established in C57BL/6 mice. At the 4th week of feeding, a pharmacologic inhibitor of gut-derived 5-HT synthesis LP533401 (12.5 mg/kg/day), simvastatin (SIM) (5 mg/kg/day) and benzafibrate (BZ) (75 mg/kg/day) were administered for two weeks by oral gavage. Then, intraperitoneal glucose tolerance test (IPGTT), open field test (OFT), tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT) were used to evaluate metabolic and neurobehavioral performances. Immunohistochemical staining, real-time quantitative PCR and other methods were to explore possible mechanisms. It was found that HFD feeding and drug treatments had some significant effects on neurobehaviors and brain: (1) All administrations reduced the total cholesterol (TC) and triglyceride (TG) parametric abnormality caused by HFD. LP533401 and SIM could significantly improve the impaired glucose tolerance, while BZ had no significant effect. (2) LP533401, SIM and BZ alleviated depression-like behavior of HFD mice in OFT, TST, FST and SPT. (3) LP533401 and SIM reversed the inhibition of Tryptophan Hydroxylase 2, Tph2 gene expression and the activation of Indoleamine 2,3-dioxy-Genase, IDO expression in HFD-treated brain, whereas BZ did not. (4) LP533401, SIM and BZ restored the inhibitory expression of 5-HT1A receptor in HFD hippocampus. Conclusions: Selective inhibition of intestinal 5-HT can attenuate depressive-like behavior, reduce 5-HT1AR impairment in hippocampus and correct abnormal 5-HT pathway in brain while ameliorating HFD-induced glucose intolerance. Further experiments are warranted to define the adequate strategy of targeting peripheral 5-HT for the treatment of such co-morbidity.


High-fat diet (HFD) Peripheral 5-HT Obesity Behavioral changes Glucose intolerance Hippocampal 5-HT1A receptors 





Area under the curve


Blood-brain barrier


Brain derived neurotrophic factor




cAMP-response element binding






Forced swim test




High-fat diet


Hydroxymethylglutaryl coenzyme A


Indoleamine 2,3-dioxy-Genase


Intraperitoneal glucose tolerance test


Insulin receptor substrate-1




LDL-receptor related protein 5


Neuropeptide Y


Open Field Test


Positron Emission Computed Tomography


Peroxisome proliferator activated receptor α




Sucrose preference test


total cholesterol




Tryptophan Hydroxylase


Tail Suspension Test



This study was supported by One Hundred Person Project of The Chinese Academy of Sciences, Applied Basic Research Programs of Qinghai Province (Y229461211); Science and Technology Plan Projects in Xinjiang (2014AB043); 2017 CMA-L’OREAL China Skin/Hair Grant (No.S2017140917); Prospective Joint Research Project of Jiangsu Province (BY2016078-02); The Open Project of State Key Laboratory of Natural Medicines (No. 3144060130); The National Natural Science Foundation of China (No. 81874331) and Science and Technology Plan Projects in Qinghai Province (2015-ZJ-733).

Compliance with ethical standards

Conflict of interest

The authors have declared that there are no conflicts of interest.


  1. André C, Dinel AL et al (2014) Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation. Brain Behav Immun 41(4):10–21PubMedGoogle Scholar
  2. Arcego DM, Toniazzo AP et al (2017) Impact of high-fat diet and early stress on depressive-like behavior and hippocampal plasticity in adult male rats. Mol Neurobiol (6):1–14Google Scholar
  3. Arnold SE, Lucki I, Brookshire BR, Carlson GC, Browne CA, Kazi H, Bang S, Choi BR, Chen Y, McMullen MF, Kim SF (2014) High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice. Neurobiol Dis 67(7):79–87PubMedPubMedCentralGoogle Scholar
  4. Assies J, Pouwer F, Lok A, Mocking RJT, Bockting CLH, Visser I, Abeling NGGM, Duran M, Schene AH (2010) Plasma and erythrocyte fatty acid patterns in patients with recurrent depression: a matched case-control study. PLoS One 5:e10635PubMedPubMedCentralGoogle Scholar
  5. Balduini W, Mazzoni E et al (2003) Prophylactic but not delayed administration of simvastatin protects against long-lasting cognitive and morphological consequences of neonatal hypoxic-ischemic brain injury, reduces interleukin-1beta and tumor necrosis factor-alpha mRNA induction, and does not affect endothelial nitric oxide synthase expression. Stroke 34(8):2007–2012PubMedGoogle Scholar
  6. Bertrand PP, Bertrand RL (2010) Serotonin release and uptake in the gastrointestinal tract. Auton Neurosci 153(1–2):47–57PubMedGoogle Scholar
  7. Blednov YA, Benavidez JM, Black M, Ferguson LB, Schoenhard GL, Goate AM, Edenberg HJ, Wetherill L, Hesselbrock V, Foroud T, Adron Harris R (2015) Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcohol Clin Exp Res 39(1):136–145PubMedGoogle Scholar
  8. Boitard C, Cavaroc A, Sauvant J, Aubert A, Castanon N, Layé S, Ferreira G (2014) Impairment of hippocampal-dependent memory induced by juvenile high-fat diet intake is associated with enhanced hippocampal inflammation in rats. Brain Behav Immun 40:9–17PubMedGoogle Scholar
  9. Budni J, Gadotti VM, Kaster MP, Santos ARS, Rodrigues ALS (2007) Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test. Eur J Pharmacol 575(1–3):87–93PubMedGoogle Scholar
  10. Buydensbranchey L, Branchey M, Hudson J, Fergeson P (2000) Low HDL cholesterol, aggression and altered central serotonergic activity. Psychiatry Res 93:93–102Google Scholar
  11. Can ÖD, Ulupınar E et al (2012) The effect of simvastatin treatment on behavioral parameters, cognitive performance, and hippocampal morphology in rats fed a standard or a high-fat diet. Behav Pharmacol 23(5):582–592PubMedGoogle Scholar
  12. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007a) Metabolic Endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772PubMedGoogle Scholar
  13. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM (2007b) Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50(11):2374–2383PubMedGoogle Scholar
  14. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57(6):1470–1481PubMedGoogle Scholar
  15. Carr GV, Lucki I (2011) The role of serotonin receptor subtypes in treating depression: a review of animal studies. Psychopharmacology 213(2–3):265–287PubMedGoogle Scholar
  16. Chalon S, Delion-Vancassel S, Belzung C, Guilloteau D, Leguisquet AM, Besnard JC, Durand G (1998) Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. J Nutr 128:2512–2519PubMedGoogle Scholar
  17. Cunha MP, Pazini FL, Oliveira Á, Machado DG, Rodrigues ALS (2013) Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice. Brain Res Bull 95:61–69PubMedGoogle Scholar
  18. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56PubMedPubMedCentralGoogle Scholar
  19. Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NMJ, Magness S, Jobin C, Lund PK (2010) High-fat diet: Bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 5(8):e12191PubMedPubMedCentralGoogle Scholar
  20. Dunbar JA, Reddy P, Davis-Lameloise N, Philpot B, Laatikainen T, Kilkkinen A, Bunker SJ, Best JD, Vartiainen E, Kai Lo S, Janus ED (2008) Depression: an important comorbidity with metabolic syndrome in a general population. Diabetes Care 31(12):2368–2373PubMedPubMedCentralGoogle Scholar
  21. Elbatsh MM (2015) Antidepressant-like effect of simvastatin in diabetic rats. Can J Physiol Pharmacol 93(8):649–656PubMedGoogle Scholar
  22. Ferguson LB, Most D, Blednov YA, Harris RA (2014) PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption. Neuropharmacology 86(1):397–407PubMedPubMedCentralGoogle Scholar
  23. Freemantle E, Chen GG, Cruceanu C, Mechawar N, Turecki G (2013) Analysis of oxysterols and cholesterol in prefrontal cortex of suicides. Int J Neuropsychopharmacol 16:1241–1249PubMedGoogle Scholar
  24. Gershon MD (2013) 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 20(1):14–21PubMedPubMedCentralGoogle Scholar
  25. Gul S, Saleem D, Haleem MA, Haleem DJ (2017) Inhibition of hormonal and behavioral effects of stress by tryptophan in rats. Nutr Neurosci:1–9Google Scholar
  26. Haleem DJ (2014) Investigations into the involvement of leptin in responses to stress. Behav Pharmacol 25(5–6):384PubMedGoogle Scholar
  27. Hao JX, Han M et al (2012) Relationship between intestinal mucosal inflammation and mental disorders in patients with irritable bowel syndrome. Zhonghua Yi Xue Za Zhi 92(32):2247–2251PubMedGoogle Scholar
  28. Ismail K, Winkley K, Stahl D, Chalder T, Edmonds M (2007) A cohort study of people with diabetes and their first foot ulcer: the role of depression on mortality. Diabetes Care 30(6):1473–1479PubMedGoogle Scholar
  29. Jr CW, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF (2005) Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry 57:343–350Google Scholar
  30. Kan C, Silva N, Golden SH, Rajala U, Timonen M, Stahl D, Ismail K (2013) A systematic review and meta-analysis of the association between depression and insulin resistance. Diabetes Care 36(2):480–489PubMedPubMedCentralGoogle Scholar
  31. Kaneko H, Goto H (2013) Functional gastrointestinal disorders (FGID): progress in diagnosis and treatments. Topic II. Current status and future prospective of medical care of the representative disorders; 4. Pathophysiology, diagnosis and treatment of irritable bowel syndrome. Nihon Naika Gakkai Zasshi 102(1):70–76PubMedGoogle Scholar
  32. Karsenty G, Gershon MD (2011) The importance of the gastrointestinal tract in the control of bone mass accrual. Gastroenterology 141(2):439–442PubMedPubMedCentralGoogle Scholar
  33. Kaufman J, Delorenzo C et al (2016) The 5-HT1A receptor in major depressive disorder. Eur Neuropsychopharmacol 26(3):397–410PubMedPubMedCentralGoogle Scholar
  34. Kawada T (2013) Comment on: Pan et al. bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes care 2012;35:1171–1180. Diabetes Care 36(2):E27–E27PubMedPubMedCentralGoogle Scholar
  35. Kellum JM, Donowitz M, Cerel A, Wu J (1984) Acid and isoproterenol cause serotonin release by acting on opposite surfaces of duodenal mucosa. J Surg Res 36(2):172–176PubMedGoogle Scholar
  36. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder. JAMA 289(23):3095–3105PubMedGoogle Scholar
  37. Kim DY, Camilleri M (2000) Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol 95(10):2698–2709PubMedGoogle Scholar
  38. Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T (2010) Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of MicroRNA-448-mediated repression of KLF5. Mol Endocrinol 24(10):1978–1987PubMedPubMedCentralGoogle Scholar
  39. Knol MJ, Twisk JW et al (2006) Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 49(5):837–845PubMedGoogle Scholar
  40. Krevvata M, Silva BC, Manavalan JS, Galan-Diez M, Kode A, Matthews BG, Park D, Zhang CA, Galili N, Nickolas TL, Dempster DW, Dougall W, Teruya-Feldstein J, Economides AN, Kalajzic I, Raza A, Berman E, Mukherjee S, Bhagat G, Kousteni S (2014) Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood 124(18):2834–2846PubMedPubMedCentralGoogle Scholar
  41. Krishna S, Lin Z, de la Serre CB, Wagner JJ, Harn DH, Pepples LM, Djani DM, Weber MT, Srivastava L, Filipov NM (2016) Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake. Physiol Behav 157:196–208PubMedPubMedCentralGoogle Scholar
  42. Lim SW, Shiue YL, Liao JC, Wee HY, Wang CC, Chio CC, Chang CH, Hu CY, Kuo JR (2017) Simvastatin therapy in the acute stage of traumatic brain injury attenuates brain trauma-induced depression-like behavior in rats by reducing Neuroinflammation in the Hippocampus. Neurocrit Care 26(1):122–132PubMedGoogle Scholar
  43. Lin PY, Huang SY, Su KP (2010) A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry 68:140–147PubMedGoogle Scholar
  44. Lin PY, Chang AY et al (2014) Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress. Pharmacol Biochem Behav 124(124):174–179PubMedGoogle Scholar
  45. Liu Q, Yang Q, Sun W, Vogel P, Heydorn W, Yu XQ, Hu Z, Yu W, Jonas B, Pineda R, Calderon-Gay V, Germann M, O'Neill E, Brommage R, Cullinan E, Platt K, Wilson A, Powell D, Sands A, Zambrowicz B, Shi ZC (2008) Discovery and characterization of novel tryptophan hydroxylase inhibitors that selectively inhibit serotonin synthesis in the gastrointestinal tract. J Pharmacol Exp Ther 325(1):47–55PubMedGoogle Scholar
  46. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BWJH, Zitman FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67(3):220PubMedGoogle Scholar
  47. Lustman PJ, Clouse RE (2005) Depression in diabetic patients: the relationship between mood and glycemic control. J Diabetes Complicat 19(2):113–122PubMedGoogle Scholar
  48. Magliano DC, Bargut TC et al (2013) Peroxisome proliferator-activated receptors-alpha and gamma are targets to treat offspring from maternal diet-induced obesity in mice. PLoS One 8(5):e64258PubMedPubMedCentralGoogle Scholar
  49. Manev H, Manev R (2007) 5-lipoxygenase as a possible biological link between depressive symptoms and atherosclerosis. Arch Gen Psychiatry 64(11):1333PubMedGoogle Scholar
  50. Manocha M, Shajib MS, Rahman MM, Wang H, Rengasamy P, Bogunovic M, Jordana M, Mayer L, Khan WI (2013) IL-13-mediated immunological control of enterochromaffin cell hyperplasia and serotonin production in the gut. Mucosal Immunol 6(1):146–155PubMedGoogle Scholar
  51. Martin AM, Young RL, Leong L, Rogers GB, Spencer NJ, Jessup CF, et al (2017) The diverse metabolic roles of peripheral serotonin. Endocrinology 158(5):1049–1063Google Scholar
  52. Oh C-M, Namkung J, Go Y, Shong KE, Kim K, Kim H, Park B-Y, Lee HW, Jeon YH, Song J, Shong M, Yadav VK, Karsenty G, Kajimura S, Lee I-K, Park S, Kim H (2015) Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nat Commun 6 (1).
  53. Orth M, Bellosta S (2012) Cholesterol: its regulation and role in central nervous system disorders. Cholesterol 2012:292598PubMedPubMedCentralGoogle Scholar
  54. Papazoglou IK, Jean A, Gertler A, Taouis M, Vacher CM (2015) Hippocampal GSK3β as a molecular link between obesity and depression. Mol Neurobiol 52(1):363–374PubMedGoogle Scholar
  55. Porsolt RD, Le Pichon M et al (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266(5604):730–732PubMedGoogle Scholar
  56. Santos T, Baungratz MM et al (2012) Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression. Neuropsychiatr Dis Treat 8(8):413–422PubMedPubMedCentralGoogle Scholar
  57. Schachter M (2005) Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol 19(1):117–125PubMedGoogle Scholar
  58. Schachter J, Martel J et al (2017) Effects of obesity on depression: a role for inflammation and the gut microbiota. Brain Behav ImmunGoogle Scholar
  59. Sharma S, Fulton S (2013) Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry. Int J Obes 37(3):382–389Google Scholar
  60. Shi ZC, Devasagayaraj A, Gu K, Jin H, Marinelli B, Samala L, Scott S, Stouch T, Tunoori A, Wang Y, Zang Y, Zhang C, Kimball SD, Main AJ, Sun W, Yang Q, Nouraldeen A, Yu XQ, Buxton E, Patel S, Nguyen N, Swaffield J, Powell DR, Wilson A, Liu Q (2008) Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders. J Med Chem 51(13):3684–3687PubMedGoogle Scholar
  61. Sierra S, Ramos MC et al (2010) Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. J Alzheimers Dis 23(2):307–318Google Scholar
  62. Skilton MR, Moulin P, Terra JL, Bonnet F (2007) Associations between anxiety, depression, and the metabolic syndrome. Biol Psychiatry 62(11):1251–1257PubMedGoogle Scholar
  63. Stockmeier CA (2003) Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 37(5):357–373PubMedGoogle Scholar
  64. Stunes AK, Reseland JE, Hauso Ø, Kidd M, Tømmerås K, Waldum HL, Syversen U, Gustafsson BI (2011) Adipocytes express a functional system for serotonin synthesis, reuptake and receptor activation. Diabetes Obes Metab 13(6):551–558PubMedGoogle Scholar
  65. Sumara G, Sumara O, Kim JK, Karsenty G (2012) Gut-derived serotonin is a multifunctional determinant to fasting adaptation. Cell Metab 16(5):588–600PubMedPubMedCentralGoogle Scholar
  66. Terasawa T, Aso Y, Omori K, Fukushima M, Momobayashi A, Inukai T (2015) Bezafibrate, a peroxisome proliferator-activated receptor α agonist, decreases circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes. Transl Res 165(2):336–345PubMedGoogle Scholar
  67. Tiemeier H, Van DW et al (2004) Relationship between atherosclerosis and late-life depression: the Rotterdam study. Arch Gen Psychiatry 61(4):369PubMedGoogle Scholar
  68. Valassi E, Scacchi M, Cavagnini F (2008) Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 18(2):158–168PubMedGoogle Scholar
  69. Valladolidacebes I, Fole A et al (2013) Spatial memory impairment and changes in hippocampal morphology are triggered by high-fat diets in adolescent mice. Is there a role of leptin? Neurobiol Learn Mem 106(6):18–25Google Scholar
  70. Vancassel S, Leman S, Hanonick L, Denis S, Roger J, Nollet M, Bodard S, Kousignian I, Belzung C, Chalon S (2008) N-3 polyunsaturated fatty acid supplementation reverses stress-induced modifications on brain monoamine levels in mice. J Lipid Res 49:340–348PubMedGoogle Scholar
  71. Vanner SJ, Meerveld GV et al (2006) Fundamentals of Neurogastroenterology: basic science. Gastroenterology 130(5):1391–1411Google Scholar
  72. Vevera J, Žukov I, Morcinek T, Papežová H (2003) Cholesterol concentrations in violent and non-violent women suicide attempters. Eur Psychiatry 18:23–27PubMedGoogle Scholar
  73. Vevera J, Valeš K, Fišar Z, Hroudová J, Singh N, Stuchlík A, Kačer P, Nekovářová T (2016) The effect of prolonged simvastatin application on serotonin uptake, membrane microviscosity and behavioral changes in the animal model. Physiol Behav 158:112–120PubMedGoogle Scholar
  74. Wang H, Steeds J, Motomura Y, Deng Y, Verma-Gandhu M, el-Sharkawy RT, McLaughlin JT, Grencis RK, Khan WI (2007) CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection. Gut 56(7):949–957PubMedPubMedCentralGoogle Scholar
  75. Wang KW, Chen HJ et al (2014) Simvastatin attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. Ann Clin Lab Sci 44(2):145–150PubMedGoogle Scholar
  76. Wang J, Liu Y, Li L, Qi Y, Zhang Y, Li L, Teng L, Wang D (2017a) Dopamine and serotonin contribute to Paecilomyces hepiali against chronic unpredictable mild stress induced depressive behavior in Sprague Dawley rats. Mol Med Rep 16(4):5675–5682PubMedGoogle Scholar
  77. Wang H, Zhou J et al (2017b) Simvastatin and Bezafibrate ameliorate emotional disorder induced by high fat diet in C57BL/6 mice. Sci Rep 7(1)Google Scholar
  78. Wu HL, Pang SL, Liu QZ, Wang Q, Cai MX, Shang J (2014) 5-HT1A/1B receptors as targets for optimizing pigmentary responses in C57BL/6 mouse skin to stress. PLoS One 9:e89663PubMedPubMedCentralGoogle Scholar
  79. Wu H, Feng J, Lv W, Huang Q, Fu M, Cai M, He Q, Shang J (2016) Developmental neurotoxic effects of percutaneous drug delivery: behavior and neurochemical studies in C57BL/6 mice. PLoS One 11(9):e0162570PubMedPubMedCentralGoogle Scholar
  80. Wu H, Liu Q, Kalavagunta PK, Huang Q, Lv W, An X, Chen H, Wang T, Heriniaina RM, Qiao T, Shang J (2018) Normal diet vs high fat diet - a comparative study: behavioral and neuroimmunological changes in adolescent male mice. Metab Brain Dis 33:177–190PubMedGoogle Scholar
  81. Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G (2008) Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135(5):825–837PubMedPubMedCentralGoogle Scholar
  82. Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P (2010) Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med 16(3):308–312PubMedPubMedCentralGoogle Scholar
  83. Zemdegs J, Quesseveur G, Jarriault D, Pénicaud L, Fioramonti X, Guiard BP (2016) High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice. Br J Pharmacol 173(13):2095–2110PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Qi Pan
    • 1
    • 2
    • 3
  • Qiongzhen Liu
    • 1
    • 2
  • Renling Wan
    • 1
    • 2
    • 3
  • Praveen Kumar Kalavagunta
    • 1
    • 2
    • 3
  • Li Liu
    • 1
    • 2
    • 3
  • Wenting Lv
    • 1
    • 2
    • 3
  • Tong Qiao
    • 4
  • Jing Shang
    • 1
    • 2
    • 3
    • 5
    Email author
  • Huali Wu
    • 1
    • 6
    Email author
  1. 1.State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjingChina
  2. 2.Jiangsu Key Laboratory of TCM Evaluation and Translational ResearchChina Pharmaceutical UniversityNanjingChina
  3. 3.School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjingChina
  4. 4.Vascular Surgery DepartmentNanjing Drum Tower HospitalNanjingChina
  5. 5.Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, NorthwestXiningChina
  6. 6.Department of PharmacologyChina Pharmaceutical UniversityNanjingChina

Personalised recommendations