Neostriatal and mesolimbic neurons: Dose-dependent effects of clozapine

G. V. Rebec, T. R. Bashore, K. S. Zimmerman, Kevin Alloway

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)281-288
Number of pages8
JournalNeuropharmacology
Volume19
Issue number3
DOIs
StatePublished - Mar 1980

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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