title: Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.
abstract: We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline α2 receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. These results suggest that tipepidine exerts an antidepressant-like effect in the forced swimming test in ACTH-treated rats, and that the effect of tipepidine is mediated by the stimulation of dopamine D1 receptors and adrenaline α2 receptors. The results also suggest that an increase in the extracellular dopamine level in the NAc may be involved in the antidepressant-like effect of tipepidine in ACTH-treated rats.
authors.affiliation: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawaura
authors.affiliation: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Sokichi
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Soeda
authors.affiliation: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shirasaki
authors.affiliation: Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan. Electronic address: takahama@kumamoto-hsu.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahama
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001552:Benzazepines / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D007099:Imipramine / Q000627:therapeutic use; D046353:Immobility Response, Tonic / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming / Q000523:psychology*
chemical_list: D000928:Antidepressive Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D006728:Hormones; D010880:Piperidines; C534628:SCH 23390; D012702:Serotonin Antagonists; C028458:tipepidine; D000324:Adrenocorticotropic Hormone; D007099:Imipramine; D010134:Fenclonine
keywords: Antitussive; Dopamine; G protein-coupled inwardly rectifying potassium channel; Tipepidine; Treatment-resistant depression