Diazepam impairs place learning in naive but not in maze-experienced rats in the Morris water maze

Abstract

Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.

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

“…Our finding that NSP rats can learn the location of the hidden platform under DZP as readily as controls is similar to findings of Zanotti et al (1994) but unlike those of McNamara and Whishaw (1990). Zanotti found that DZP did not affect reversal learning in the water maze in rats first spatially trained with no drug.…”

Effects of Δ9-THC and WIN-55,212-2 on place preference in the water maze in rats

“…1988;Acquas et al 1989;Borsini et al 1993;Gray et al 1999) or has no effect (Meririnne et al 1999;Leri and Franklin 2000;Matsuzawa et al 2000). Induction of place preference is in sharp contrast to the spatial learning impairments in the water maze (Zanotti et al 1994).…”

Effects of CRF1 receptor antagonists and benzodiazepines in the Morris water maze and delayed non-matching to position tests

“…Cognitive tasks involving visual-spatial ability are especially vulnerable to the effects of benzodiazepines (Golombok et al 1988), and in preclinical studies the acquisition of spatial mapping tasks such as the Morris water maze have proven to be very sensitive to the cognitive deficits produced by benzodiazepines (McNaughton and Morris 1987;Arolfo and Brioni 1991;McNamara and Skelton 1991;Zanotti et al 1994). The Morris water maze is also sensitive to the beneficial effects produced by CRF agonists (Behan et al 1995;Zorrilla et al 2002), so the Morris water maze was included in the present experiments to assess the effects of benzodiazepines and CRF 1 receptor antagonists on cognitive function.…”