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 e nhance cognitive performance in a variety of learning paradigms. This prompted us to examine the effects of some more potent and newly synth esised GABA(B) antagonists CGP 71982, CGP 62349 and CGP 55845A in an a ctive avoidance test in rats. A two-way active avoidance test with neg ative reinforcement was performed for the first 5 of 12 days of antago nist administration. CGP 71982 and CGP 55845A at all doses applied (0. 01-1.0 mg/kg) had an improving effect on learning, and memory retentio n on day 12; the rats made more avoidances in both sessions compared t o controls. CGP 62349 was only active at the lowest dose tested (0.01 mg/kg). The present study confirms that GABA(B) receptor antagonists c an enhance cognitive performance but provides no insight into the mech anism of action of these novel antagonists.