In conclusion, GABAB receptors enable GABA to modulate neuronal function in a manner not possible through GABAA receptors alone. These receptors are present at both pre- and postsynaptic sites and can exert both inhibitory and disinhibitory effects. In particular, GABAB receptors are important in regulating NMDA receptor-mediated responses, including the induction of LTP. They also can regulate the filtering properties of neural networks, allowing peak transmission in the frequency range of theta rhythm. Finally, GABAB receptors are G protein-coupled to a variety of intracellular effector systems, and thereby have the potential to produce long-term changes in the state of neuronal activity, through actions such as protein phosphorylation. Although the majority of the effects of GABAB receptors have been reported in vitro, recent studies have also demonstrated that GABAB receptors exert electrophysiological actions in vivo. For example, GABAB receptor antagonists reduce the late IPSP in vivo and consequently can decrease inhibition of spontaneous neuronal firing following a stimulus (Lingenhöhl and Olpe, 1993). In addition, blockade of GABAB receptors can increase spontaneous activity of central neurons, suggesting the presence of GABAB receptor-mediated tonic inhibition (Andre et al., 1992; Lingenhöhl and Olpe, 1993). Despite these electrophysiological effects, antagonism of GABAB receptors has generally been reported to produce few behavioral actions. This lack of overt behavioral effects most likely reflects the modulatory nature of the receptor action. Nevertheless, two separate behavioral studies have recently reported an enhancement of cognitive performance in several different animal species following blockade of GABAB receptors (Mondadori et al., 1992; Carletti et al., 1993). Because of their small number of side effects, GABAB receptor antagonists may represent effective therapeutic tools for modulation of cognition. Alternatively, the lack of overt behavioral effects of GABAB receptors may indicate that these receptors are more important in pathologic rather than normal physiological states (Wojcik et al., 1989). For example, a change in receptor affinity or receptor number brought on by the pathology could enhance the effectiveness of GABAB receptors. Of significance, CGP 35348 has been shown to block absence seizures in genetically seizure prone animals, while inducing no seizures in control animals (Hosford et al., 1992; Liu et al., 1992). Thus, GABAB receptors may represent effective sites for pharmacological regulation of absence seizures. Perhaps further behavioral effects of these receptors will become apparent only after additional studies have been performed using the highly potent antagonists that have been recently introduced.(ABSTRACT TRUNCATED AT 400 WORDS)