Kolisnyk_2015_Br.J.Pharmacol_172_4919

BACKGROUND AND PURPOSE: Disruptions of executive function, including attentional deficits, are a hallmark of a number of diseases. ACh in the prefrontal cortex regulates attentive behaviour; however, the role of alpha7 nicotinic ACh receptor (alpha7nAChR) in attention is contentious. EXPERIMENTAL APPROACH: In order to probe attention, we trained both wild-type and alpha7nAChR knockout mice on a touch screen-based five-choice serial reaction time task (5-CSRT). Following training procedures, we then tested sustained attention using a probe trial experiment. To further differentiate the role of specific nicotinic receptors in attention, we then tested the effects of both alpha7nAChR and beta2nAChR agonists on the performance of both wild-type and knockout mice on the 5-CSRT task. KEY
RESULTS: At low doses, alpha7nAChR agonists improved attentional performance of wild-type mice, while high doses had deleterious effects on attention. alpha7nAChR knockout mice displayed deficits in sustained attention that were not ameliorated by alpha7nAChR agonists. However, these deficits were completely reversed by the administration of a beta2nAChR agonist. Furthermore, administration of a beta2nAChR agonist in alpha7nAChR knockout mice elicited similar biochemical response in the prefrontal cortex as the administration of alpha7nAChR agonists in wild-type mice. CONCLUSIONS AND IMPLICATIONS: Our experiments reveal an intricate relationship between distinct nicotinic receptors to regulate attentional performance and provide the basis for targeting beta2nAChRs pharmacologically to decrease attentional deficits due to a dysfunction in alpha7nAChRs.