Chronic treatment with clozapine selectively decreases basal dopamine release in nucleus accumbens but not in caudate-putamen as measured by in vivo brain microdialysis: further evidence for depolarization block.
As measured using in vivo brain microdialysis in conscious freely-moving rats, chronic treatment (20 mg/kg/day i.p. for 21 days) with the clinically atypical neuroleptic clozapine selectively reduced basal dopamine (DA) release in the nucleus accumbens (Acb) but not in caudate-putamen (CPu). Apomorphine (100 micrograms/kg s.c.) enhanced presynaptic Acb DA release in clozapine-treated rats, but reduced Acb DA release in vehicle-treated rats. These findings provide further evidence that depolarization block of mesolimbic DA neurons projecting to Acb but not of nigrostriatal DA neurons projecting to CPu may underlie clozapine's unusual clinical efficacy and its lack of production of extrapyramidal motoric effects.
Chen
J P
JP
Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461.
Paredes
W
W
Gardner
E L
EL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D009467:Neuromuscular Depolarizing Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D003024:Clozapine; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid