Prior non-spatial pretraining eliminates sensorimotor disturbances and impairments in water maze learning caused by diazepam.

Diazepam has been reported to impair spatial learning in the water maze. This experiment reexamined this topic using control groups that had first been non-spatially pretrained to familiarize them with the general behavioral strategies required in the water maze task. Naive rats given diazepam (0.5, 3.0, 6.0 mg/kg, IP) displayed dose-related maze acquisition impairments and sensorimotor disturbances (swimming in the periphery of the pool, deflecting off or swimming over the hidden platform, jumping off the platform when placed there after a trial, ataxia on a narrow wooden beam). The sensorimotor disturbances interfered with the acquisition of information about the spatial location of the platform, occurred in the absence of impairments in a subsequent visible platform task or swim speed, and correlated strongly with measures of acquisition. In contrast, the non-spatially pretrained groups did not exhibit sensorimotor disturbances in the water maze and acquired the maze task as rapidly under diazepam as control rats. The non-spatially pretrained groups continued to display diazepam-induced sensorimotor disturbances (ataxia) in a novel beam walking task. CGS8216 (10.0 or 20.0 mg/kg), a benzodiazepine receptor antagonist, attenuated the effect of 3.0 or 6.0 mg/kg diazepam in naive rats, suggesting that the effects of diazepam were mediated by benzodiazepine receptors. Occupancy of benzodiazepine receptors by diazepam does not prevent robust spatial learning in the water maze.