RESUMO
In order to understand the underlying mechanisms responsible for the behaviors mediated by dextromethorphan (DM), we examined the effects of DM on locomotor activity and locomotor patterns in mice, and Fos-related antigen immunoreactivity (FRA-IR) of mouse brain following repeated administration of cocaine. Combined treatments (30 min prior to each cocaine administration) with DM dose-dependently decreased locomotor activity for high doses of cocaine (20 mg/kg, i.p./day x 7). DM combinations did not significantly affect hyperactivity for 10 mg cocaine/kg, i.p./day x 7. In contrast, combined treatments with DM increased the locomotor activity for 5 mg cocaine/kg, i.p./day x 7. These results were consistent with alterations in marginal activity. Repeated administration with cocaine or DM increased FRA-IR in the nucleus accumbens (NAc) and striatum which lasted for at least 7 days. Our results suggest that DM exhibits biphasic effects on the locomotor stimulation induced by cocaine, and that locomotor activities are in parallel with FRA-IR of the striatal complex. However, the role of FRA-IR regulated by DM or/and cocaine remains to be further determined.
Assuntos
Antitussígenos/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cocaína/farmacologia , Dextrometorfano/farmacologia , Atividade Motora/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/biossíntese , Animais , Encéfalo/metabolismo , Cocaína/administração & dosagem , Dextrometorfano/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Dextromethorphan (DM) at supra-antitussive doses might produce psychotomimetic effects in humans. In order to understand the underlying mechanisms responsible for the behavior induced by DM, we examined the effects of DM on cocaine-induced conditioned place preference (CPP) and locomotor pattern in mice, and Fos-related antigen immunoreactivity (FRA-IR) in the striatal complex (nucleus accumbens and striatum) of the mouse brain. The effects of DM (20 and 40 mg/kg, i.p.) on the CPP for 2.5, 5, 10, and 20 mg cocaine/kg, i.p. were assessed. Pretreatment with DM dose-dependently decreased the CPP for 20 mg cocaine/kg. Similarly, pretreatment with DM appeared to reduce the CPP for 10 mg cocaine/kg, but increase the CPP for 5 mg cocaine/kg. This finding was more pronounced for 2.5 mg cocaine/kg; DM significantly increased the CPP for 2.5 mg cocaine/kg in a dose-related manner. Furthermore, these results were correlated with alterations in the locomotor pattern (marginal activity) and FRA-IR in the striatal complex. Thus, our results suggest that DM exhibits a biphasic effect on the cocaine-induced CPP and locomotor pattern.