Involvement of serotonin receptor subtypes in the antidepressant-like effect of TRIM in the rat forced swimming test.
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.
Ulak
Güner
G
Department of Pharmacology, Faculty of Medicine, Kocaeli University, 41380 Kocael, Turkey. gunerulak@yahoo.com
Mutlu
Oguz
O
Tanyeri
Pelin
P
Komsuoglu
F Ipek
FI
Akar
Füruzan Yildiz
FY
Erden
B Faruk
BF
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007103:Immobilization; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D013550:Swimming
D000928:Antidepressive Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011985:Receptors, Serotonin; C098107:flibanserin; D052248:Nitric Oxide Synthase Type I