The GABA(B) receptor antagonist CGP36742 attenuates the baclofen- and scopolamine-induced deficit in Morris water maze task in rats.

Effects of CGP36742 (3-aminopropyl-n-butylphosphinic acid), an orally active GABA(B) receptor antagonist, on the baclofen- and scopolamine-induced deficit of place learning in the Morris water maze task were examined in rats. Rats were given four training trials per day with the submerged platform at a fixed location in the maze for 4 days. On day 4, the rats were required to swim in the pool without the platform after the fourth training trial (probe test). Intraperitoneal injection of baclofen (4 mg/kg) or scopolamine (0.3 mg/kg) significantly increased the escape latency to reach the platform and decreased the duration in the quadrant where the platform had been originally located. Increased latency in the training trials and decreased duration in the probe test induced by baclofen or scopolamine were significantly attenuated by oral administration of CGP36742 at doses of 10 and 30 mg/kg. In the rotarod test, CGP36742 at a dose of 100 mg/kg but not at doses of 10 or 30 mg/kg antagonized the baclofen-induced motor incoordination. Thus, there was dissociation between the effective doses of CGP36742 in the learning task and those in the sensory motor test. These results suggest the possible involvement of cholinergic systems as well as GABA(B) receptor systems in the CGP36742 action.