The effect of nitric oxide synthase inhibition on cognitive ability and strategies employed for place learning in the water maze: sex differences.

Male and female rats use different cognitive strategies in the solution of place-learning problems in the water maze despite similar abilities. The female-type strategy has been negatively correlated with cortical nitric oxide (NO) metabolites. The present study aimed to examine the effect of NO synthase (NOS) inhibition (N(omega)-nitro-L-arginine, L-NA) on cognitive ability and strategy in the water maze, and to evaluate possible sex differences. In a 2 (male versus female) x2 (L-NA versus saline) factorial design, rats were trained to find the platform (visible or hidden), always in the same position, for 12 days. L-NA impaired acquisition, during the earlier phases and more prominently in females. This impairment was quite dramatic and unique to females during the first day that the platform was hidden following 3 days of visible-platform conditions. After acquisition, the visible platform's position was shifted, thereby presenting the rats with a choice (searching for the hidden platform in the previous location, i.e. adopting a conceptual cognitive style, or escaping to the visible platform in a new position, i.e. adopting a perceptual style). On the first of the four shift trials (where the newly positioned platform was proximal to the rat's starting position), female rats showed the previously found tendency to adopt a perceptual style escape directly in clear contrast to saline-treated males. The L-NA-treated males tended to manifest female-like perceptual style, suggesting that inhibition of NO synthesis in males weakened the tendency to choose a conceptual style in this shifted-platform task. The role of NO in both cognitive and non-cognitive psychological functions is discussed.