Involvement of serotonin receptor subtypes in the antidepressant-like effect of TRIM in the rat forced swimming test

Pharmacol Biochem Behav. 2010 May;95(3):308-14. doi: 10.1016/j.pbb.2010.02.006. Epub 2010 Feb 18.

Abstract

Depression is a common illness with severe morbidity and mortality. Nitric oxide synthase (NOS) inhibitors are shown to elicit antidepressant-like effect in various animals models. It is widely known that serotonin plays an important role in the antidepressant-like effect of drugs. The aim of this study is to investigate the involvement of 5-HT(1) and 5-HT(2) receptor subtypes in the antidepressant-like effect of TRIM, a nNOS inhibitor, in the rat forced swimming test (FST). TRIM displays an antidepressant-like activity in FST which is blocked by pretreatment with the NOS substrate l-arginine. Depletion of endogenous serotonin using para-chlorophenylalanine (pCPA; 3x150mg/kg, i.p.) partially attenuated TRIM (50mg/kg)-induced reductions in immobility time in FST. Pretreatment with methiothepin (0.1mg/kg, i.p, a non-selective 5-HT receptor antagonist), cyproheptadine (3mg/kg i.p, a 5-HT(2) receptor antagonist) or ketanserin (5mg/kg i.p, a 5HT(2A/2C) receptor antagonist) prevented the effect of TRIM (50mg/kg) in the FST. WAY 100635 (0.1mg/kg i.p, a selective 5-HT(1A) receptor antagonist) and GR 127935 (3mg/kg i.p, a selective 5-HT(1B/1D) receptor antagonist) slightly reversed the immobility-reducing effect of TRIM in the FST, but this failed to reach a statistically significant level. The results of this study demonstrate that antidepressant-like effect of TRIM in the FST seems to be mediated, at least in part, by an interaction with 5-HT(2) receptors while non-significant effects were obtained with 5-HT(1) receptors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / therapeutic use
  • Depression / drug therapy*
  • Depression / enzymology
  • Depression / psychology
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Immobilization
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / physiology
  • Male
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / physiology*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / enzymology
  • Stress, Psychological / physiopathology
  • Swimming*

Substances

  • Antidepressive Agents
  • Benzimidazoles
  • Enzyme Inhibitors
  • Isoenzymes
  • Receptors, Serotonin
  • flibanserin
  • Nitric Oxide Synthase Type I