Pre- and postsynaptic GABAB receptors of rat neocortical neurons differ in their pharmacological properties

GABA (gamma-amino butyric acid)B receptors have been proposed to play a dual role in synaptic transmission in the mammalian central nervous system (CNS): they participate in a late inhibitory postsynaptic potential (1-IPSP) and reduce the release of GABA by a presynaptic action. To further characterize these mechanisms, two established GABAB receptor antagonists were applied to intracellularly recorded rat neocortical neurons in vitro. The depression of the 1-IPSP by the GABAB receptor antagonists phaclofen and 2-OH-saclofen averaged 30% and 50%, respectively. Phaclofen had no effect on direct excitability or excitatory synaptic transmission. The depression of a second IPSP evoked by paired-pulse stimulation was used as an index for presynaptic GABAB receptor activation. Neither antagonist exerted significant effects on this transient depression of GABAergic inhibition. The present results suggest that the pre- and postsynaptic GABAB receptors involved in GABAergic transmission of neocortical neurons differ in their pharmacological properties.