The modulatory effects of high affinity GABAB receptor antagonists in an active avoidance learning paradigm in rats

It has been reported that selective GABA_B receptor antagonists can enhance cognitive performance in a variety of learning paradigms. This prompted us to examine the effects of some more potent and newly synthesised GABA_B antagonists CGP 71982, CGP 62349 and CGP 55845A in an active avoidance test in rats. A two-way active avoidance test with negative reinforcement was performed for the first 5 of 12 days of antagonist administration. CGP 71982 and CGP 55845A at all doses applied (0.01–1.0 mg/kg) had an improving effect on learning, and memory retention on day 12; the rats made more avoidances in both sessions compared to controls. CGP 62349 was only active at the lowest dose tested (0.01 mg/kg). The present study confirms that GABA_B receptor antagonists can enhance cognitive performance but provides no insight into the mechanism of action of these novel antagonists. Received: 4 August 1997/Final version: 28 November 1997