5-HT3 RECEPTOR ANTAGONIST MDL-72222 DOSE-DEPENDENTLY ATTENUATES COCAINE-INDUCED AND AMPHETAMINE-INDUCED ELEVATIONS OF EXTRACELLULAR DOPAMINE IN THE NUCLEUS-ACCUMBENS AND THE DORSAL STRIATUM

The effects of a 5-HT3 receptor antagonist MDL 72222 on cocaine- and a mphetamine-induced increases in extracellular dopamine in the nucleus accumbens and the dorsal striatum were studied with microdialysis tech nique using halothane anaesthesized rats. Dopamine and its metabolites were measured by HPLC with electrochemical detection. Cocaine elevate d extracellular dopamine in the nucleus accumbens and to a lesser exte nt in the dorsal striatum, but it did not affect dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. Pretrea tment with MDL 72222 (25-100 mu g/kg) dose-dependently attenuated coca ine-induced elevation of dopamine in both of the nuclei studied. Amphe tamine elevated extracellular dopamine and reduced DOPAC and homovanil lic acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also attenuated the amphetamine-induced elevation of extrace llular dopamine concentration in both brain areas studied, but first a t a dose of 100 mu g/kg. The different potencies of the interactions o f the 5-HT3 receptor antagonist with cocaine and amphetamine could be related to the different mechanisms by which these drugs primarily ele vate extracellular dopamine.