Nicotinic-serotonergic drug interactions and attentional performance in rats

Both central serotonergic and nicotinic systems play important roles in a variety of neurobehavioral functions; however, the interactions of these two systems have not been fully characterized. The current study served to determine the impact of a relatively selective 5-HT2A receptor antagonist, ketanserin, on attentional function in rats and the interactions of ketanserin with nicotine administration.

A standard operant visual signal detection task was used to assess sustained attention. In expt 1, adult female Sprague-Dawley rats (n = 39) were injected subcutaneously (SC) with a dose range of ketanserin (0, 0.25, 0.5 and 1 mg/kg). In expt 2, the interactions of acute ketanserin (0, 1 and 2 mg/kg, SC) and acute nicotine (0, 25 and 50 microg/kg, SC) were assessed. In expt 3, the interaction of acute ketanserin (0, 1 and 2 mg/kg, SC) and chronic nicotine (5 mg/kg per day, SC for 4 weeks via osmotic pump) was characterized. Using an operant visual signal detection task, three possible outcomes (dependent variables) were measured in each trial: percent hit, percent correct rejection, and response omissions.

Ketanserin, when given alone, did not have a significant effect on either percent hit or percent correct rejection. Acute administration of 25 microg/kg nicotine significantly improved percent hit (i.e. improvement in choice accuracy), an effect that was reversed by acute administration of 1 mg/kg ketanserin. Chronic nicotine infusion for 28 consecutive days significantly increased percent correct rejection (i.e. improvement in choice accuracy) without development of tolerance, an effect which was reversed by an acute dose of 2 mg/kg ketanserin.

These data suggest a functional interaction between nicotine and 5-HT2A receptor antagonist ketanserin.