Differential effects of amfonelic acid on the haloperidol- and clozapine-induced increase in extracellular DOPAC in the nucleus accumbens and the striatum.
This study compares the effects of the nonamphetamine stimulant amfonelic acid on the increase in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) induced by haloperidol and clozapine in the nucleus accumbens and the striatum of anaesthetized rats. DOPAC was simultaneously recorded in both regions using differential pulse voltammetry with electrically pretreated carbon fibre electrodes. Amfonelic acid (2.5 mg/kg s.c.) did not alter basal striatal DOPAC but produced a significant reduction in extracellular DOPAC in the nucleus accumbens. Haloperidol (1 mg/kg s.c.) increased extracellular DOPAC in both regions. When amfonelic acid was injected 5 min before haloperidol, the increase in DOPAC was potentiated in both the nucleus accumbens and the striatum but with a greater effect in the striatum. Clozapine (30 mg/kg i.p.) increased extracellular DOPAC in both regions, an effect partially attenuated by amfonelic acid in both regions but to a greater extent in the striatum. When ritanserin (5 mg/kg i.p.), a serotonergic antagonist (5-HT-2), was co-administered with haloperidol, the potentiation by amfonelic acid of the increase in extracellular DOPAC induced by haloperidol was attenuated in both the nucleus accumbens and the striatum. The present results confirm that amfonelic acid can be used to discriminate neurochemically between haloperidol and clozapine in vivo. The effects of amfonelic acid on the neuroleptic-induced changes in extracellular DOPAC were greater in the striatum than the nucleus accumbens. These results further demonstrate that both neuroleptics increase dopamine metabolism in the two brain regions but by different mechanisms, supporting the view that the regulation of dopamine metabolism differs in the two regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Medical School, University of Sherbrooke, Quebec, Canada.
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Rivest
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Marsden
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D016713:Ritanserin / Q000494:pharmacology; D013997:Time Factors
D009287:Naphthyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D016713:Ritanserin; D009268:Nalidixic Acid; D006897:Hydroxyindoleacetic Acid; D003024:Clozapine; D006220:Haloperidol; C006486:amfonelic acid