Effects of acute and chronic clozapine and haloperidol administration on 3-methoxytyramine accumulation in rat prefrontal cortex, nucleus accumbens and striatum.
The accumulation of 3-methoxytyramine (3-MT), a reflection of dopamine release, was measured in the prefrontal cortex, nucleus accumbens, and striatum following administration of acute and chronic clozapine and haloperidol. Several doses of each drug were used. The effects of chronic drug treatment were measured 1 h (chronic 1 h groups), 24 h (chronic 24 h groups) and 48 h (chronic 48 h groups) after the final dose of each drug. In the prefrontal cortex, clozapine and haloperidol elevated 3-MT more in the acute groups than in the chronic 1 h groups, suggesting that partial tolerance developed. In the striatum and nucleus accumbens, acute and chronic (chronic 1 h) haloperidol produced equal increases in 3-MT above the appropriate baselines, suggesting that no tolerance developed. In the striatum, clozapine reduced 3-MT in the chronic 1 h group after high doses (25 mg/kg), and in the chronic 24 h group. These results suggest that neuroleptics may not produce the reduction in dopamine release that has been predicted with the development of depolarization inactivation. The reduction of striatal dopamine release during chronic clozapine treatment may be related to clozapine not being associated with the development of tardive dyskinesia.
Egan
M F
MF
National Institute of Mental Health, St. Elizabeths Hospital, Washington, DC 20032.
Karoum
F
F
Wyatt
R J
RJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002849:Chromatography, Gas; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003024:Clozapine; D006220:Haloperidol; C001746:3-methoxytyramine; D004298:Dopamine