Nicotine provokes impulsive-like action by stimulating α4β2 nicotinic acetylcholine receptors in the infralimbic, but not in the prelimbic cortex

Nicotine, a major addictive component of tobacco, has been suggested to provoke impulsivity by activating central alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs). Although lesion studies have demonstrated the involvement of the medial prefrontal cortex (mPFC) in impulsive action, the precise brain sites responsible for nicotine-induced impulsive action have not been identified. Our goal was to determine whether alpha 4 beta 2 nAChRs in the prelimbic cortex (PL) and/or infralimbic cortex (IL), which are subregions of the mPFC, mediate nicotine-induced impulsive-like action in the three-choice serial reaction time task (3-CSRTT). The 3-CSRTT is a simple version of five-choice serial reaction time task and a rodent model of impulsive action in which the animal is required to inhibit the response until a light stimulus is presented randomly in one of three holes. Following the completion of the training, rats were bilaterally injected with dihydro-beta-erythroidine (DH beta E; 6 and 18 mu g/side), a selective alpha 4 beta 2 nAChRs antagonist, into the PL or IL before systemic injection of nicotine (0.2 mg/kg, salt, s.c.). Intra-IL DH beta E infusions dose-dependently blocked nicotine-induced impulsive-like action, while infusions of DH beta E into the PL failed to block the effects of nicotine on impulsive-like action. The present results suggest a critical role for alpha 4 beta 2 nAChRs in the IL in mediating the effects of nicotine on impulsive-like action in the 3-CSRTT.