To determine whether clozapine, an antipsychotic drug devoid of extrapyramidal side effects, acts preferentially on neurons in the nucleus accumbens rather than in the neostriatum, an analysis of clozapine-induced changes in spontaneous neuronal activity was performed on locally anesthetized, immobilized rats. In both brain sites, intraperitoneal administration of clozapine (10, 20 or 80 mg/kg) produced a comparable dose-dependent increase in neuronal activity. Haloperidol, at a dose (2.0mg/kg) that typically elicits extrapyramidal side effects in rats, also increased the firing rate of neurons in the neostriatum and nucleus accumbens. However, haloperidol produced a greater effect on neuronal activity in the neostriatum during the first 15 min after injection, whereas 80 mg/kg clozapine was more effective during this period in the nucleus accumbens. In contrast, the neuronal response to the lower doses of clozapine paralleled that produced by haloperidol in the neostriatum; no differential regional effects were recorded at any time after injection of 10 or 20 mg/kg clozapine. The results suggest that the lack of extrapyramidal side effects associated with clozapine cannot be simply explained by a selective action of this drug on neurons in the nucleus accumbens.
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience