Hippocampal long-term potentiation and spatial learning in the rat: Effects of GABA(B) receptor blockade

This series of experiments assessed the role of GABA(B) receptors in the induction of long-term potentiation in the dentate gyrus in vivo, and spatial learning and memory in three different tasks. In urethane-anesthetized rats, the GABA(B) receptor antagonist CGP 46381 was injected intraperitoneally at a dose which effectively suppressed GABA(B)-mediated paired pulse disinhibition. Theta-burst stimulation reliably produced long-term potentiation in control rats. However, GABA(B) receptor blockade significantly suppressed the induction of long-term potentiation in the dentate gyrus. To compare the results of the long-term potentiation experiments with behavior, we assessed the performance of rats on several spatial learning and memory tasks in the presence of CGP 46381. We found that the working memory performance of highly trained rats on the eight-arm radial maze was unaffected by CGP 46381. There was also no effect of GABA(B) receptor blockade on learning in the eight-arm maze using a five-trial repeated acquisition paradigm. However, when we tested spatial learning in naive rats using a mildly stressful water maze task, we found that CGP 46381 substantially impaired both the latency to find the platform and the pathlength travelled in the maze during acquisition. CGP 46381-treated rats took longer to learn the location of the escape platform and travelled a greater distance over the acquisition trials. These data demonstrate that GABA(B) receptor blockade results in a suppression of hippocampal long-term potentiation in vivo and impairs spatial learning in a task where stress may be a component of performance.