Endogenous acetylcholine modulates impulsive action via α4β2 nicotinic acetylcholine receptors in rats

Nicotine has been well established as an impulsive action-inducing agent, but it remains unknown whether endogenous acetylcholine affects impulsive action via nicotinic acetylcholine receptors. In the present study, the 3-choice serial reaction time task (3-CSRTT), a simple and valid assessment of impulsive action, was employed. Male Wistar/ST rats were trained to detect and respond to 1-s flashes of light presented in one of three holes until stable performance was achieved. Following training on the 3-CSRTT, rats received intracerebroventricular injections of the preferential a4 beta 2 nicotinic acetylcholine receptor antagonist dihydro-beta-erythroidine (DH beta E; 0, 3, 10, and 30 mu g) or the selective alpha 7 nicotinic acetylcholine receptor antagonist methyllycaconitine (MLA: 0, 3, 10, and 30 mu g) 5 min before test sessions. Injection of 10 mu g of DH beta E significantly suppressed premature responses, an index of impulsive-like action, without changing other behavioral parameters. On the other hand, MLA infusions failed to affect impulsive-like action at any dose. These results suggest that the central a4 beta 2 nicotinic acetylcholine receptors that enable a provoking effect of endogenous acetylcholine play a critical role in impulsive action. Substances that modulate nicotinic acetylcholine receptors, especially the WIN subtype, may be beneficial for the treatment of psychiatric disorders characterized by lack of inhibitory control. (C) 2010 Elsevier B.V. All rights reserved.