title: Clozapine does activate nigrostriatal dopamine neurons in unanesthetized rats.
abstract: Antipsychotic drugs are traditionally classified as typical or atypical on the basis of their property to cause or not to cause extrapyramidal side-effects. A widely accepted selectivity for the mesolimbic, vs. the nigrostriatal, dopaminergic system is postulated to underlie the existence of fewer or no extrapyramidal side-effects during treatment with atypical neuroleptics. In order to verify this hypothesis we examined the effect of acute clozapine on nigrostriatal dopaminergic neurons recorded from non-anaesthetised and from chloral hydrate-anaesthetised rats. Extracellular single-unit recording coupled with antidromic activation from the neostriatum was used. Intravenous administration of cumulative doses of clozapine (1.25-10 mg/kg) increased the firing rate of nigrostriatal dopaminergic neurons in non-anaesthetised rats, but failed to significantly modify the activity of the same units under chloral hydrate anesthesia. These results indicate that acute clozapine activates nigrostriatal dopamine cells in non-anaesthetised rats and cast doubts about a direct link between the lack of significant extrapyramidal side-effects and the selectivity of atypical neuroleptics, such as clozapine, for the mesolimbic dopamine system.
authors.affiliation: B.B. Brodie Department of Neuroscience, University of Cagliari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Melis
authors.forename: G L
authors.initials: GL
authors.lastname: Gessa
authors.forename: M
authors.initials: M
authors.lastname: Diana
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D004298:Dopamine