Differential Effects of Nicotinic Acetylcholine Receptor Stimulation on Negative Occasion Setting

We have previously shown that nicotine enhances learning in a negative occasion setting task in which rats are trained to distinguish between two different trial types. During reinforced trials, a target stimulus (a tone) is presented and immediately followed by food reward. On nonreinforced trials, a feature stimulus (a light) is presented prior to the tone and indicates the absence of reward following presentation of the tone. The goal of the present study was to identify the behavioral mechanism through which nicotine affects this form of learning, and to determine which subtype(s) of nicotinic acetylcholine receptors mediate the effects of nicotine. Consistent with our prior findings, nicotine administration enhanced the ability of rats to discriminate between the two trial types. Nicotine enhanced the magnitude of the discrimination by decreasing responding to the tone on nonreinforced trials. Nicotine-treated rats also learned the discrimination in fewer sessions than control rats. A significant new finding was that nicotine also increased the orienting response to the light, suggesting that nicotine may enhance learning the serial feature negative discrimination by increasing attention to the visual feature. In addition, we found that RJR-2403, a selective alpha 4 beta 2 nicotinic receptor agonist, also enhanced discrimination. However, RJR-2403 did not affect responding on nonreinforced trials, nor did RJR-2403 affect orienting to the light. Together these data indicate that nicotine may enhance discrimination by enhancing tone-reward associability through alpha 4 beta 2 nicotinic receptors and by enhancing attention to the light through non-alpha 4 beta 2 receptor subtypes.