Nicotine provokes impulsive-like action by stimulating alpha4beta2 nicotinic acetylcholine receptors in the infralimbic, but not in the prelimbic cortex.
BACKGROUND
Nicotine, a major addictive component of tobacco, has been suggested to provoke impulsivity by activating central alpha4beta2 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.


OBJECTIVE
Our goal was to determine whether alpha4beta2 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).


METHODS
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 (DHbetaE; 6 and 18 microg/side), a selective alpha4beta2 nAChRs antagonist, into the PL or IL before systemic injection of nicotine (0.2 mg/kg, salt, s.c.).


RESULTS
Intra-IL DHbetaE infusions dose-dependently blocked nicotine-induced impulsive-like action, while infusions of DHbetaE into the PL failed to block the effects of nicotine on impulsive-like action.


CONCLUSIONS
The present results suggest a critical role for alpha4beta2 nAChRs in the IL in mediating the effects of nicotine on impulsive-like action in the 3-CSRTT.
Tsutsui-Kimura
Iku
I
Department of Neuropharmacology, Graduate School of Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo, 060-8638, Japan.
Ohmura
Yu
Y
Izumi
Takeshi
T
Yamaguchi
Taku
T
Yoshida
Takayuki
T
Yoshioka
Mitsuhiro
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine