?-Hydroxybutyric acid (GHBA) induces pacemaker activity and inhibition of substantia nigra dopamine neurons by activating GABAB-receptors

Abstract

In the present study the actions of gamma-hydroxybutyric acid (GHBA) on dopaminergic neurons in the rat substantia nigra (SN) were pharmacologically analysed utilising extracellular single unit recording techniques. Intravenous administration of GHBA was associated with several effects on the neuronal activity of nigral dopamine (DA) neurons. Low doses (< 200 mg/kg) of GHBA produced a slight excitation of the neurons, concomitant with a regularized firing rhythm and lack of burst activity. In higher doses GHBA produced an even higher degree of regularization but, in contrast to low doses, an inhibition of firing rate. Administration of the GABAB-receptor agonist baclofen, in all essential respects, mimicked the effect of GHBA on the firing of nigral DA neurons. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic administration of GHBA were antagonised by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). Our observations show that GHBA affects the firing pattern of nigral DA neurons in doses considerably lower than those required to inhibit the firing rate of the neurons. This action, as well as the decreased firing rate observed after high doses of GHBA, are mediated via activation of GABAB-receptors.