Muscarinic antagonists attenuate the increase in accumbens and striatum dopamine metabolism produced by clozapine but not by haloperidol.
1. The effect of the muscarinic antagonists, scopolamine and atropine, were examined on the increase in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum induced by haloperidol and clozapine by use of in vivo differential pulse voltammetry with carbon fibre electrodes in anaesthetized rats. 2. Animals received saline (1 ml kg-1, s.c.), scopolamine (1 mg kg-1, o.p.) or atropine (20 micrograms, i.c.v.) followed 15 min later by saline (10 microliters, i.c.v.), haloperidol (1 mg kg-1, s.c.) or clozapine (30 mg kg-1, i.p.) and extracellular DOPAC was simultaneously recorded in the nucleus accumbens and the striatum every 5 min for 60 min after drug administration. 3. Scopolamine or atropine alone had no effect on the DOPAC peak height but attenuated the increase in extracellular DOPAC induced by clozapine in both brain regions. Neither scopolamine nor atropine altered the haloperidol-induced increase in accumbens or striatal extracellular DOPAC. 4. The present results demonstrate that muscarinic antagonists attenuate the increase in accumbens and striatal dopamine metabolism in vivo produced by the atypical neuroleptic clozapine but not the haloperidol-induced increase in dopamine metabolism. The results indicate that central muscarinic receptors are involved in the actions on dopaminergic function of clozapine but not haloperidol.
Rivest
R
R
Department of Pharmacology, Medical School, University of Sherbrooke, Quebec, Canada.
Marsden
C A
CA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000494:pharmacology
D010276:Parasympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D001285:Atropine; D012601:Scopolamine; D003024:Clozapine; D006220:Haloperidol; D004298:Dopamine