Opposite effects of depressant and convulsant barbiturate stereoisomers on acetylcholine release from the rat hippocampus in vivo

Abstract

Background. It has been shown that the R(-) isomer of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) induces loss of the righting reflex (LRR), while S(+)-MPPB causes pure excitatory effects, including convulsions, in vivo. Methods. We studied the effects of the depressant and convulsant MPPB stereoisomers on rat hippocampal acetylcholine (ACh) release in vivo, using a brain microdialysis technique in freely moving animals. Results. R(-)-MPPB 60 and 90 mg kg-1 i.p. decreased ACh release from the rat hippocampus by 44.1 (8.2)% and 60.8 (8.2)%, respectively. In the hippocampus, the local application of bicuculline, a γ-aminobutyric acid (GABA)A receptor antagonist, 1 μmol litre-1 antagonized the inhibitory effects of R(- -MPPB 90 mg kg-1 i.p. In contrast, R(-)-MPPB, S(+)-MPPB 60 and 90 mg kg-1 i.p. increased ACh release to 151.8 (6.8)% and 169.6 (11.1)% of the basal release, respectively. Conclusions. Our results demonstrated that R(-)-MPPB decreased, while S(+)-MPPB increased, rat hippocampal ACh release and that the inhibitory effects of R(-)-MPPB may involve the GABAA receptor in vivo. These data imply that changes in hippocampal ACh due to these agents may be related to their central inhibitory and stimulatory actions in vivo. © The Board of Management and Trustees of the British Journal of Anaesthesia 2004.