Acute administration of clozapine, thioridazine and metoclopramide increases extracellular DOPAC and decreases extracellular 5-HIAA, measured in the nucleus accumbens and striatum of the rat using in vivo voltammetry.
Changes in the extracellular levels of dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indoleacetic acid (5-HIAA) after acute administration of clozapine (50 mg/kg s.c.), thioridazine (20 mg/kg s.c.) and metoclopramide (5 mg/kg s.c.), were monitored using in vivo voltammetry with micro-carbon electrodes implanted in the nucleus accumbens and striatum of the rat anaesthetised with halothane/N2O. Both clozapine and thioridazine increased extracellular levels of DOPAC in the striatum and the nucleus accumbens. The maximum increases with clozapine were 60% and 86% in the nucleus accumbens and striatum and 44% and 55% with thioridazine. Both neuroleptics also decreased the extracellular level of 5-HIAA in these regions of the brain. Metoclopramide increased the extracellular level of DOPAC in the nucleus accumbens (42%) and the striatum (57%) and significantly decreased the level of 5-HIAA in the nucleus accumbens. These results suggest that the two so-called atypical neuroleptics, clozapine and thioridazine, do not have selective effects on the metabolism of dopamine in vivo in the nucleus accumbens after acute administration. Furthermore, neuroleptic-induced increases in dopamine metabolism are accompanied by reciprocal decreases in 5-hydroxytryptamine metabolism in vivo.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003984:Dibenzazepines / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010648:Phenylacetates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*; D013881:Thioridazine / Q000494:pharmacology*
D003984:Dibenzazepines; D010648:Phenylacetates; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D003024:Clozapine; D008787:Metoclopramide; D013881:Thioridazine