D2 receptor-mediated inhibition of GABA release by endogenous dopamine in the rat globus pallidus

Abstract

Attempting to better understand the role of the dopaminergic innervation in the rat globus pallidus, we examined here whether or not endogenous dopamine modulates the release of [ 3H]GABA in superfused pallidal slices. The superfusion medium contained elevated (15 mM) potassium. The release of endogenous dopamine was induced by the dopamine releaser drug, methamphetamine. Methamphetamine (100 μM) inhibited by 46% the release of [ 3H]GABA. Methamphetamine inhibition was completely blocked by reserpinization of the rats. It was also completely blocked by the D2 dopamine receptor antagonist sulpiride (10 μM). Sulpiride alone caused a 105% increase in GABA release. The increase was not observed in slices from reserpinized rats. Quinpirole (10 μM), a D2 dopamine receptor agonist, inhibited (43%) [ 3H]GABA release. The results suggest that endogenous dopamine exerts an inhibitory effect on GABA release in the rat globus pallidus. The effect is mediated by D2 receptors presumably located on striatopallidal axon terminals.