Effects of dextromethorphan on nocturnal behavior and brain c-Fos expression in adolescent rats

Dextromethorphan, an antitussive widely available over-the-counter, is abused, mostly by teenagers at high doses. In our previous report, a high dose of dextromethorphan activated the midbrain dopamine neurons of adolescent rats. In the present study, we performed c-Fos immunohistochemistry in the dopaminergic terminal regions of adolescent rat brain after the intraperitoneal administration of dextromethorphan at different doses (0, 10, 20, and 40 mg/kg), and also examined the effects on nocturnal behavior. The results showed that dextromethorphan increased c-Fos expression dose dependently in the anterior cingulate cortex, caudate putamen, nucleus accumbens, and central amygdala. Significant ataxia occurred and both locomotor and rearing activity decreased immediately after the dextromethorphan injection. We conclude that the neurons in the reward pathway of the adolescent rat brain appear to be activated by a single injection of dextromethorphan, and that activation of this pathway by dextromethorphan may correlate with the behavioral effects and abuse potential of the drug.