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 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.
Erhardt
S
S
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Nissbrandt
H
H
Engberg
G
G
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D007700:Kinetics; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009025:Morpholines / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D009118:Muscimol; D007736:Kynurenic Acid; D001418:Baclofen; D004298:Dopamine