Dextromethorphan affects cocaine-mediated behavioral pattern in parallel with a long-lasting Fos-related antigen-immunoreactivity.

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.

Dual effects of dextromethorphan on cocaine-induced conditioned place preference in mice.

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.