title: Pharmacological mechanisms of antidepressant-like effect of tipepidine in the forced swimming test.
abstract: We previously reported that the centrally acting non-narcotic antitussive, tipepidine, produces a novel antidepressant-like effect in the forced swimming test in rats, but the mechanism of the antidepressant-like effect of tipepidine is not clear. We investigated the pharmacological mechanism of the antidepressant-like effect of tipepidine in the forced swimming test in rats. A catecholamine-depleting agent, alpha-methyl-p-tyrosine (AMPT; 300 mg/kg, s.c.), was given 6h before the first injection and with the last injection of tipepidine (40 mg/kg, i.p.). A serotonin (5-HT)-depleting agent, p-chlorophenylalanine (PCPA; 350 mg/kg, i.p.), was given 72 h and 48 h before the pretest session. The dopamine D(1) receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) was given 15min before each of the three injections of tipepidine. The dopamine D(2) receptor antagonist raclopride (0.2mg/kg, s.c.), the alpha 1 adrenoceptor antagonist prazosin (1mg/kg, i.p.), the alpha 2 adrenoceptor antagonist yohimbine (2mg/kg, i.p.) and the beta adrenoceptor antagonist propranolol (2mg/kg, i.p.) were given 30 min before each of the three injections of tipepidine. AMPT, but not PCPA, significantly inhibited the immobility time-reducing effect of tipepidine in the forced swimming test. Furthermore, the effect of tipepidine was significantly inhibited by SCH23390 and yohimbine. However, raclopride, prazosin, and propranolol failed to block the effect of tipepidine. The results suggest that the antidepressant-like effect of tipepidine in the forced swimming test may be due at least in part to the effects of dopamine and noradrenaline released at the dopamine D(1) receptor and alpha 2 adrenoceptor, respectively.
authors: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors: Kazuaki
authors: K
authors: Kawaura
authors: Risa
authors: R
authors: Miki
authors: Yuri
authors: Y
authors: Urashima
authors: Ryo
authors: R
authors: Kawahara
authors: Fumio
authors: F
authors: Soeda
authors: Tetsuya
authors: T
authors: Shirasaki
authors: Kazuo
authors: K
authors: Takahama
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015016:Yohimbine / Q000494:pharmacology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D001552:Benzazepines; D010880:Piperidines; C534628:SCH 23390; C028458:tipepidine; D015016:Yohimbine; D020891:Raclopride; D019805:alpha-Methyltyrosine; D011433:Propranolol; D010134:Fenclonine; D011224:Prazosin