Activation of nigral dopamine neurons by the selective GABA(B)-receptor antagonist SCH 50911

Previous studies have shown that systemic as well as local administration o f the GABA(B)-receptor agonist baclofen is associated with a decrease in fi ring rate, a regularisation of firing rhythm and a decrease in burst firing activity of dopamine (DA) containing midbrain neurons. In the present elec trophysiological study we have utilised the novel, selective and potent GAB A(B)-receptor antagonist SCH 50911 in order to further analyse the importan ce of GABA(B)-receptors for the overall activity of rat nigral DA neurons. SCH 50911 given intravenously (1-64 mg/kg) or locally, by microiontophoreti c techniques, was found to increase firing rate and to increase the burst f iring activity of DA neurons. The present data suggest that the GABA(B)-rec eptor antagonist blocks somatodendritic receptors on nigral DA neurons. Thi s 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 Park inson's disease.