Characterization of pre- and postsynaptic actions of (-)-baclofen in the guinea-pig hippocampus in vitro.

The effects of (-)-baclofen on evoked potentials in the hippocampus were examined through intracellular recordings from guinea-pig brain slices. The evoked responses were recorded in two fibre connections within the hippocampus: the Schaffer collateral/commissural-CA1 pyramidal cell, and the mossy fibre-CA3 pyramidal cell. The Schaffer collateral/commissural-CA1 response was suppressed by (-)-baclofen in concentrations over 2 X 10(-5)M, whereas (+)-baclofen, an inactive isomer, in a concentration of 10(-4)M had no effect on the response. A compound action potential of Schaffer collateral/commissural axons was unaffected by (-)-baclofen even at 10(-4)M, a concentration that almost completely depressed the evoked response in the CA1 pyramidal cell. The mossy fibre-CA3 response was not inhibited by (-)-baclofen (10(-4)M). The depressant action of (-)-baclofen on the Schaffer collateral/commissural-CA1 response was unaffected by bicuculline (10(-4)M), whereas the direct membrane effects of (-)-baclofen were antagonized by bicuculline (10(-5)M). It is suggested that (-)-baclofen may modulate neuronal transmission through presynaptic recognition sites possibly by decreasing transmitter release from nerve terminals and also may directly regulate the endogenous neuronal excitability through an activation of the postsynaptic recognition sites.