Clonidine Reduces Dopamine and Increases GABA in the Nucleus Accumbens: An In Vivo Microdialysis Study

Abstract

The effects of clonidine, an α 2 adrenoceptor agonist, on extracellular concentrations of dopamine and γ-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied by using in vivo brain microdialysis. Clonidine (5 μg/kg IV) significantly decreased the brain 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 μg/kg IV), an α 2-adrenoceptor antagonist, which itself did not affect the efflux of dopamine. A smaller dose of clonidine (1 μg/kg IV), which had no significant effect on dopamine efflux per se, decreased the dopamine efflux (21% reduction) when given together with an ineffective dose of midazolam (0.075 mg/kg IV), a benzodiazepine receptor agonist. The effect of clonidine (5 μg/kg IV) on mesolimbic dopamine efflux was abolished by bicuculline (1 mg/kg IV), a GABA A receptor antagonist, counteracted by β-carboline-3-carboxylate ethyl ester (β-CCE, 3 mg/kg IP), a benzodiazepine receptor inverse agonist, but not affected by flumazenil (6 μg/kg IV), a benzodiazepine receptor antagonist. Clonidine (5 μg/kg IV) increased the dialysate concentration of GABA in the nucleus accumbens up to a maximum of 250% at its peak effect, but not in the ventral tegmental area. It is hypothesized that GABA A binding sites in the nucleus accumbens form part of the sequence of events that is triggered by clonidine in an α 2-adrenergic-specific manner and that ultimately results in a decreased release of dopamine in the nucleus accumbens.