GAMMA-HYDROXYBUTYRIC ACID (GHBA) INDUCES PACEMAKER ACTIVITY AND INHIBITION OF SUBSTANTIA-NIGRA DOPAMINE NEURONS BY ACTIVATING GABA(B)-RECEPTORS

In the present study the actions of gamma-hydroxybutyric acid (GHBA) o n dopaminergic neurons in the rat substantia nigra (SN) were pharmacol ogically analysed utilising extracellular single unit recording techni ques. Intravenous administration of GHBA was associated with several e ffects on the neuronal activity of nigral dopamine (DA) neurons. Low d oses (< 200 mg/kg) of GHBA produced a slight excitation of the neurons , concomitant with a regularised firing rhythm and lack of burst activ ity. In higher doses GHBA produced an even higher degree of regularisa tion but, in contrast to low doses, an inhibition of firing rate. Admi nistration of the GABA(B)-receptor agonist baclofen, in all essential respects, mimicked the effect of GHBA on the firing of nigral DA neuro ns. Both the regularisation of the firing pattern and inhibition of fi ring rate produced by systemic administration of GHBA were antagonised by the GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v.). Our o bservations show that GHBA affects the firing pattern of nigral DA neu rons in doses considerably lower than those required to inhibit the fi ring rate of the neurons. This action, as well as the decreased firing rate observed after high doses of GHBA, are mediated via activation o f GABA(B)-receptors.