RESUMO
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.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Hormônios/farmacologia , Piperidinas/uso terapêutico , Natação/psicologia , Animais , Benzazepinas/farmacologia , Depressão/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Fenclonina/farmacologia , Imipramina/uso terapêutico , Resposta de Imobilidade Tônica/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Antagonistas da Serotonina/farmacologiaRESUMO
The antidepressant-like effect of tipepidine was studied in rats. Tipepidine at 20 and 40 mg/kg i.p. reduced immobility in the forced swimming test and tipepidine at 40 mg/kg, i.p. increased climbing in the test. The drug at 40 mg/kg, i.p. had no effect on the locomotor activity and motor coordination. These results suggest that tipepidine may be a novel drug with antidepressant-like activity.
