Neurobehavioral evidence for mesolimbic specificity of action by clozapine: studies using electrical intracranial self-stimulation.
The ability of chronic treatment with the atypical neuroleptic clozapine to induce functional dopaminergic hypersensitivity in laboratory rats was assessed. The intracranial electrical self-stimulation paradigm, known to be sensitive to changes in functional dopaminergic sensitivity, was used. Animals with electrodes in the ventral tegmental nucleus (mesolimbic dopamine cell body area) showed a marked increase in self-stimulation rate following 3 weeks of chronic clozapine. This increase was similar in magnitude and duration to that shown by animals given 3 weeks of chronic haloperidol. In contrast, animals with electrodes in the substantia nigra (nigrostriatal dopamine cell body area) showed no change in self-stimulation rate following 3 weeks of chronic clozapine. These data are interpreted in the light of previous suggestions that clozapine and other atypical neuroleptics may possess functional selectivity for the mesolimbic dopamine system.
D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012653:Self Stimulation / Q000187:drug effects*
D003984:Dibenzazepines; D011954:Receptors, Dopamine; D003024:Clozapine