BRAIN-DERIVED PEPTIDES INHIBIT SYNAPTIC TRANSMISSION VIA PRESYNAPTIC GABA(B) RECEPTORS IN CA1 AREA OF RAT HIPPOCAMPAL SLICES

GABA(B) receptors form the basis of a powerful and versatile inhibitor y system in the mammalian brain. Presynaptic and postsynaptic actions of GABA(B) receptors have been described in various brain regions, inc luding the hippocampus. We report here on a novel pharmacological agen t, presumably a peptide, which inhibits synaptic transmission in the C A1 area of the rat hippocampus via GABA(B) receptors. The agent is a c omponent of a nootropic drug, Cerebrolysin(TM), obtained from pig's br ain extract. In contrast to other, presently known agonists, such as b aclofen or GABA, Cerebrolysin(TM) acts preferentially on presynaptic G ABA(A) receptors and has no detectable postsynaptic inhibitory effects . Additional, postsynaptic depolarizing action of the drug resulting i n increased excitability is pharmacologically distinct from the GABA(B ) response and partially masked by the inhibition. The presynaptic GAB A(B) agonist may add to clinical effects of Cerebrolysin(TM) in treatm ent of brain injuries. Moreover, it promises to be a useful experiment al agent in further studies of many possible functional roles of GABA( B) receptors.