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 α4β2 nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine (DHβE; 0, 3, 10, and 30 μg) or the selective α7 nicotinic acetylcholine receptor antagonist methyllycaconitine (MLA; 0, 3, 10, and 30 μg) 5 min before test sessions. Injection of 10 μg of DHβE 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 α4β2 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 α4β2 subtype, may be beneficial for the treatment of psychiatric disorders characterized by lack of inhibitory control.