The effects of alpha1A adrenergic receptor knockout on learning, memory, and seizure incidence (845.2)

Abstract

The role of the α1 adrenergic receptor (α1ARs) subtypes, α1A‐ and α1BAR, in the central nervous system is not well understood. Specifically, there are conflicting data regarding the role of the α1AR in learning and memory, possibly because agonists and antagonists highly selective for each subtype are not available. Our lab has used transgenic and chronic pharmacologic models of activation to examine the role of the α1AAR subtype in modulating seizure threshold, learning, and memory. Previously, we found that stimulation of the α1AAR subtype has positive effects. When exposed to flurothyl, transgenic animals overexpressing the α1AAR (CAM‐α1AAR mice) have an increased seizure threshold when compared with wild type (WT) mice. CAM‐α1AAR and mice treated with the α1AAR agonist cirazoline have enhanced spatial learning when compared with WT animals. Stimulation of the α1AAR also increases proliferation in the adult mouse dentate gyrus, which has been linked to enhanced learning in other studies. In the current study, α1AAR knock‐out (A‐KO) mice were used to determine the effects on learning and memory in the Barnes maze, Morris water maze, and novel object recognition task. An assessment of general health and neurological reflexes did not show any abnormalities in the A‐KO mice. The A‐KO mice did not spend more time with the novel object than chance would dictate, suggesting impaired recognition memory. In the Barnes maze, A‐KO mice took significantly longer to solve the maze than WT mice. The Morris water maze is ongoing but, thus far, no differences in learning have been observed. A subset of A‐KO mice experienced novelty‐induced seizures during the testing period; the data will be examined for effects of seizures on learning ability.