gamma-Hydroxybutyric acid and baclofen decrease extracellular acetylcholine levels in the hippocampus via GABA(B) receptors.
The effect of gamma-hydroxybutyric acid (GHB) and baclofen, a GABA(B) receptor agonist, on extracellular hippocampal acetylcholine levels was studied in freely moving rats by microdialysis. GHB (200 and 500 mg/kg, i.p.) reduced in a dose-dependent manner, extracellular hippocampal acetylcholine concentrations and this effect was prevented by the GABA(B) receptor antagonist (2S)(+)-5,5-Dimethyl-2-morpholineacetic acid (SCH 50911), at the dose of 20 mg/kg (i.p.), while the putative GHB receptor antagonist 6,7,8,9-Tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS 382) was ineffective. Similar to GHB, the GABA(B) agonist baclofen (10 and 20 mg/kg, i.p.) produced a dose-related reduction in extracellular acetylcholine concentrations which was prevented by SCH 50911. These findings indicate that GHB-induced reduction of hippocampal acetylcholine release is mediated by GABA(B) receptors and support a possible involvement of hippocampal GABA(B) receptors in the control of cognitive processes and in the claimed amnesic effect of GHB intoxication.
Nava
F
F
Department of Neuroscience "Bernard B. Brodie", University of Cagliari, Cagliari, Italy. felnava@tin.it
Carta
G
G
Bortolato
M
M
Gessa
G L
GL
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology*; D001567:Benzocycloheptenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D013997:Time Factors
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D000927:Anticonvulsants; D001567:Benzocycloheptenes; D018755:GABA Agonists; D018756:GABA Antagonists; D006885:Hydroxybutyrates; D009025:Morpholines; D018080:Receptors, GABA-B; C066471:NCS 382; C111420:4-hydroxybutyric acid; D001418:Baclofen; D000109:Acetylcholine