Ketanserin attenuates nicotine-induced working memory improvement in rats

Nicotinic systems have been shown in numerous studies to be important for spatial working memory. Nicotinic systems are certainly not acting alone in the basis of memory function, but act in concert with a variety of other neural systems. Important for these interactions is nicotinic induced release of a variety of neurotransmitters involved in memory function including serotonin (5-HT). We have found that the 5-HT2 receptor antagonist, ketanserin, effectively attenuated nicotine-induced attentional improvement. The current study explored the interaction between nicotinic and serotonergic systems in the performance of a spatial working memory task in the radial-arm maze. Female Sprague-Dawley rats were trained on the win-shift working memory task on the 8-arm radial maze. After 18 sessions of acquisition training the rats were given acute doses of nicotine (0.2 and 0.4 mg/kg), ketanserin (0.5, 1 and 2 mg/kg) or combinations of the two. The vehicle served as the control. As seen in previous studies, nicotine caused a significant improvement in working memory performance as indexed by the number of correct arm entries before the first error (entries to repeat). Ketanserin at the doses tested did not cause a significant effect on choice accuracy, but it did significantly attenuate the improvement caused by the 0.2 mg/kg nicotine dose. The higher 0.4 mg/kg nicotine dose was nearly sufficient to overcome the ketanserin effect. This study shows that, as with attentional function, nicotine-induced working memory improvement is attenuated by the 5-HT2 antagonist ketanserin. Given that many antipsychotic drugs have substantial 5-HT2 antagonist effects, these atypical antipsychotic drugs may reduce the cognitive improvements caused by nicotinic treatments.