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

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 GABA_A 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.