Abstract
Previous studies have shown that systemic as well as local administration of the GABA(B)-receptor agonist baclofen is associated with a decrease in firing rate, a regularisation of firing rhythm and a decrease in burst firing activity of dopamine (DA) containing midbrain neurons. In the present electrophysiological study we have utilised the novel, selective and potent GABA(B)-receptor antagonist SCH 50911 in order to further analyse the importance of GABA(B)-receptors for the overall activity of rat nigral DA neurons. SCH 50911 given intravenously (1-64 mg/kg) or locally, by microiontophoretic techniques, was found to increase firing rate and to increase the burst firing activity of DA neurons. The present data suggest that the GABA(B)-receptor antagonist blocks somatodendritic receptors on nigral DA neurons. This GABA-receptor input appears to be of a tonic nature. It is proposed that the activation of nigral DA neurons may underlie the beneficial effects of GABA(B)-receptor antagonists in the modulation of cognition and that GABA(B)-receptor antagonists may be of therapeutic value in the treatment of Parkinson's disease.