Stimulation parameters determine role of GABAB receptors in long-term potentiation

Blockade of GABA_B receptors was reported to improve cognitive performance in mammals. The physiological basis of this effect is poorly understood. We investigated the effect of the GABA_B receptor antagonist CGP 35348 on long-term potentiation (LTP) in the CA1 area of the hippocampus in vitro and in vivo. In vitro the effect of CGP 35348 on LTP, induced either by two non-primed tetanic stimulations or by two primed bursts of stimuli, was investigated. In the presence of 1 mM CGP 35348 LTP was significantly facilitated following two non-primed tetanic trains, but was impaired following two primed burst stimulations. In vivo LTP was induced by applying non-primed trains of stimuli of increasing duration to the Schaffer collateral/commissural fibers. The potentiation of the population spike recorded in CA1 was significantly facilitated by CGP 35348 (100 mg/kg i.v.). In conclusion these findings demonstrate that the GABA_B antagonist CGP 35348 facilitates LTP in vitro and in vivo if induced by non-primed tetanic stimulation. In vitro, the mode of stimulation determines the effect of the GABA_B antagonist on LTP.