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) rece ptor agonist, on extracelhilar hippocampal acetylcholine levels was studied in freely moving rats by microdialysis. GHB (200 and 500 mg/kg, i.p.) redu ced in a dose-dependent manner, extracellular hippocampal. acetylcholine co ncentrations and this effect was prevented by the GABA(B) receptor antagoni st (2S)(+)-5,5-Di-methyl-2-morpholineacetic acid (SCH 50911), at the dose o f 20 mg/kg (i.p.), while the putative GHB receptor antagonist 6,7,8,9-Tetra hydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS 382) was ineffe ctive. Similar to GHB, the GABA(B) agonist baclofen (10 and 20 mg/kg, i.p.) produced a dose-related reduction in extracellular acetylcholine concentra tions which was prevented by SCH 50911. These findings indicate that GHB-in duced reduction of hippocampal acetylcholine release is mediated by GABA(B) receptors and support a possible involvement of hippocampal GABA(B) recept ors in the control of cognitive processes and in the claimed amnesic effect of GHB intoxication. (C) 2001 Published by Elsevier Science B.V.