The Influence of Alpha7 and Alpha4 Beta2 Nicotinic Receptor Agonists on Feature Based Reversal Learning in Macaque Monkeys

Selective and non-selective nicotinic agonists are associated with improvements in higher order cognitive functions. However, the effects of selectively activating nicotinic sub-receptors on attention and learning are not well understood. In my project, I used two agonists selective for alpha7 (7) and alpha4-beta2 (42) nicotinic sub-receptors to test the effects of selective nicotinic activation on performance in a feature-based reversal learning task in non-human primate subjects. Overall, results showed that selective activation of nicotinic receptors led to improvements in different aspects of the task which were time and dose dependent: the optimal dose of 7 agonist improved performance accuracy and sped up learning of reversals in reward contingency, when drug plasma concentration was at its peak. In comparison, the best dose of 42 agonist reduced susceptibility to distraction. These findings are an important first step to identify the nicotinergic neuromodulatory mechanisms of attention and learning functions in the primate brain.