The effect of α-2 adrenergic agonists on memory and cognitive flexibility

Background: The noradrenergic system modulates cognitive flexibility for insight-based problem solving in studies using β-adrenergic antagonists, which block noradrenergic neurotrans-mission postsynaptically. However, it is not known whether α 2 -adrenergic agonists, that decrease noradrenergic neurotrans-mission by presynaptic inhibition, have the same effect. Objectives: Therefore, we wished to test whether α 2 -adrenergic agonists would have a similar effect on cognitive flexibility. Methods: Eighteen normal adults were tested on cognitive flexibility, problem solving, verbal and spatial memory tasks after receiving clonidine (0.1 mg), an α 2 -agonist, placebo, or ephedrine (25 mg), a noradrenergic stimulant. Results: Three-way analysis of variance revealed no significant drug effect on cognitive flexibility or problem solving. There was also no significant effect of clonidine on memory. Conclusions: Therefore, α 2 -agonists do not influence cognitive flexibility in the same manner as p-antagonists. Better performance on memory with clonidine might be expected based on primate studies demonstrating benefits in working memory using clonidine. This benefit was not observed for the commonly used clinical memory tasks in our study. This may have implications for why clonidine has not demonstrated efficacy for cognitive disorders such as Alzheimer disease, despite its known benefit for working memory in animal models.