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 t he induction of long-term potentiation in the dentate gyrus in vivo, a nd spatial learning and memory in three different tasks. In urethane-a nesthetized rats, the GABA(B) receptor antagonist CGP 46381 was inject ed intraperitoneally at a dose which effectively suppressed GABA(B)-me diated paired pulse disinhibition. Theta-burst stimulation reliably pr oduced long-term potentiation in control rats. However, GABA(B) recept or blockade significantly suppressed the induction of long-term potent iation in the dentate gyrus. To compare the results of the long-term p otentiation experiments with behavior, we assessed the performance of rats on several spatial learning and memory tasks in the presence of C GP 46381. We found that the working memory performance of highly train ed rats on the eight-arm radial maze was unaffected by CGP 46381. Ther e was also no effect of GABA(B) receptor blockade on learning in the e ight-arm maze using a five-trial repeated acquisition paradigm. Howeve r, when we tested spatial learning in naive rats using a mildly stress ful water maze task, we found that CGP 46381 substantially impaired bo th the latency to find the platform and the pathlength travelled in th e 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) recep tor blockade results in a suppression of hippocampal long-term potenti ation in vivo and impairs spatial learning in a task where stress may be a component of performance.