Potentiation of gamma-aminobutyric acid-mediated inhibition by isoproterenol in the cerebellar cortex: receptor specificity.

A large body of electrophysiological data has supported the hypothesis that an important role of norepinephrine in the central nervous system is to modulate the actions of other transmitter systems, particularly those utilizing the amino acid neurotransmitters. Noradrenergic potentiation of inhibitory responses, induced by locally-applied or synaptically-released gamma-aminobutyric acid (GABA) on cerebellar Purkinje neurons, has been observed by a number of investigators, who have suggested that activation of beta-adrenergic receptors plays a critical role in mediating this modulatory effect of norepinephrine (NE). Two postsynaptic receptors for GABA, termed A and B, have been identified and both subtypes have been found in the cerebellum of the rat. The purposes of this investigation were first to identify the subtype(s) of GABA receptor responsible for mediating the inhibitory effects of locally-applied GABA in the cerebellar cortex and second to identify which subtype of GABA receptor is modulated by a beta-adrenergic input. Inhibitory responses of cerebellar Purkinje neurons, in urethane-anesthetized rats, to iontophoretic or pressure-applied isoguvacine, a selective GABAA agonist, to baclofen, a GABAB agonist or to GABA itself, were examined before, during and after local application of isoproterenol or norepinephrine. Isoguvacine, but not baclofen, induced consistent and dose-dependent inhibition of the firing of Purkinje cells. At ejection currents that had no effect on spontaneous firing rate, iontophoretically-applied isoproterenol potentiated isoguvacine-induced inhibition. These data suggest that GABAA, rather than GABAB receptors, mediate GABA-induced inhibitions of cerebellar Purkinje neurons. Moreover, it appears that the modulation of GABA function by beta adrenergic agonists involves an interaction between a beta-adrenergic input and the GABAA receptor complex.