The effects of clozapine and fluperlapine on the in vivo release and metabolism of dopamine in the striatum and in the prefrontal cortex of freely moving rats.
The effects of the two atypical neuroleptics clozapine and fluperlapine on the dopaminergic function in the striatum and in the prefrontal cortex were studied using the transversal microdialysis technique in awake, freely moving rats. Although neither drug induced catalepsy in rats, both increased the release of dopamine (DA) and the output of its metabolites in a similar way in both areas. Unlike classical neuroleptics, after clozapine and fluperlapine administration, the stimulation of DA release was strictly coupled to that of the metabolites, and a second injection was able to renew it. Pretreatment with the selective D1 agonists SKF 38393 or CY 208-243, by themselves ineffective on the release of DA, antagonized the effects of low doses and substantially reduced those of higher doses of clozapine and fluperlapine, indicating that these two atypical drugs act, depending on the dose, selectively or partially through D1 receptors.
Imperato
A
A
Angelucci
L
L
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003984:Dibenzazepines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D014150:Antipsychotic Agents; D003984:Dibenzazepines; C041528:fluperlapine; D003024:Clozapine; D004298:Dopamine