Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by gamma-hydroxybutyric acid (GHBA) are specifically induced by activation of GABA(B) receptors.
Previous studies have shown that administration of gamma-hydroxybutyric acid (GHBA) or the GABA(B) receptor agonist baclofen are associated with a decrease in firing rate, a regularisation of firing pattern and a decrease in burst activity of midbrain dopamine (DA) neurons in the substantia nigra (SN). In the present study we compared the ability of the novel GABA(B) receptor antagonist SCH 50911 and the selective antagonist of GHBA binding sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg, i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing rhythm and the decrease of burst activity in DA cells, induced by baclofen (1-32 mg/kg, i.v.) or GHBA (12.5-1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not affect the baclofen-induced changes in neuronal activity. Neither was the drug able to influence the GHBA-induced alterations in firing rate or in burst activity, although NCS-382 to some extent antagonised the regularisation of the firing pattern observed following low doses of GHBA (< or =100 mg/kg). The results of the present study give further support for the notion that the GHBA-induced changes in neuronal activity of nigral dopamine neurons are mediated by stimulation of GABA(B) receptors.
Karolinska Institute, Department of Physiology and Pharmacology, Stockholm, Sweden.
S
S
Erhardt
B
B
Andersson
H
H
Nissbrandt
G
G
Engberg
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001567:Benzocycloheptenes / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D007478:Iontophoresis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D018080:Receptors, GABA-B / Q000187:drug effects*; D012978:Sodium Oxybate / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; C039403:4-hydroxybutyric acid receptor; D001567:Benzocycloheptenes; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D011956:Receptors, Cell Surface; D018080:Receptors, GABA-B; C066471:NCS 382; D012978:Sodium Oxybate; D001418:Baclofen; D004298:Dopamine