CLONIDINE REDUCES DOPAMINE AND INCREASES GABA IN THE NUCLEUS-ACCUMBENS - AN IN-VIVO MICRODIALYSIS STUDY

The effects of clonidine, an alpha(2) adrenoceptor agonist, on extrace llular concentrations of dopamine and gamma-aminobutyric acid (GABA) i n the nucleus accumbens of rats were studied by using in vivo brain mi crodialysis. Clonidine (5 mu g/kg IV) significantly decreased the brai n microdialysate concentration of dopamine in the nucleus accumbens up to a maximum of 16% at its peak effect. This effect was inhibited by a dose of idazoxan (10 mu g/kg TV), an alpha(2)-adrenoceptor antagonis t, which itself did not affect the efflux of dopamine. A smaller dose of clonidine (1 mu g/kg IV), which had no significant effect on dopami ne efflux per se, decreased the dopamine efflux (21% reduction) when g iven together with an ineffective dose of midazolam (0.075 mg/kg IV), a benzodiazepine receptor agonist. The effect of clonidine (5 mu g/kg IV) on mesolimbic dopamine efflux was abolished by bicuculline (1 mg/k g TV), a GABA, receptor antagonist, counteracted by beta-carboline-3-c arboxylate ethyl eater (beta-CCE, 3 mg/kg IF), a benzodiazepine recept or inverse agonist, but not affected by flumazenil (6 mu g/kg IV), a b enzodiazepine receptor antagonist. Clonidine (5 mu g/kg IV) increased the dialysate concentration of GABA in the nucleus accumbens up to a m aximum of 250% at its peak effect, but not in the ventral tegmental ar ea. It is hypothesized that GABA(A) binding sites in the nucleus accum bens form part of the sequence of events that is triggered by clonidin e in an alpha(2)-adrenergic-specific manner and that ultimately result s in a decreased release of dopamine in the nucleus accumbens. (C) 199 8 Elsevier Science Inc.