The modulatory effects of high affinity GABA(B) 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 GABAB 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.