Comparison of the effect of gamma-aminobutyric acid and its derivative baclofen on the activity of Purkinje cells of frog cerebellum in vitro.

The inhibitory effect of gamma-aminobutyric acid (GABA) and its synthetic derivative baclofen were compared in frog cerebellum in vitro. Baclofen inhibited synaptic transmission from parallel fibres to the Purkinje cells in EC50 concentrations approximately 200-fold lower than for GABA. In addition to its inhibitory effect, GABA induced temporary facilitation of responses in the dendrite zone by a mechanism dependent on the presence of a normal Cl- concentration; the inhibitory phase was only partly sensitive to reduction of the Cl- concentration in the medium and to the administration of picrotoxin. The action of baclofen, which was unaffected by these treatments, requires an intact catecholamine and serotonin pool, since it is ineffective in reserpine-treated animals. Both substances also influence the excitability of parallel fibres. In solutions with a high Mg2+ and a low Ca2+ concentrations GABA inhibits the spontaneous activity of Purkinje cells by acting on the postsynaptic membrane of the soma and the primary dendrites. The effect of baclofen is evidently the outcome of inhibition of transmitter release from presynaptic endings.