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

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Abstract

Rationale

Nicotine, a major addictive component of tobacco, has been suggested to provoke impulsivity by activating central α4β2 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.

Objectives

Our goal was to determine whether α4β2 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-β-erythroidine (DHβE; 6 and 18 μg/side), a selective α4β2 nAChRs antagonist, into the PL or IL before systemic injection of nicotine (0.2 mg/kg, salt, s.c.).

Results

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

Conclusion

The present results suggest a critical role for α4β2 nAChRs in the IL in mediating the effects of nicotine on impulsive-like action in the 3-CSRTT.

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Acknowledgments

This study was supported by a Grant from the Smoking Research Foundation (URL: http://www.srf.or.jp/english/index.html).

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Authors and Affiliations

  1. Department of Neuropharmacology, Graduate School of Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo, 060-8638, Japan

    Iku Tsutsui-Kimura, Yu Ohmura, Takeshi Izumi, Taku Yamaguchi, Takayuki Yoshida & Mitsuhiro Yoshioka

  2. Department of Pharmacology, University of Michigan, Medical School, Ann Arbor, MI, 48109-0632, USA

    Yu Ohmura

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  1. Iku Tsutsui-Kimura
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Correspondence to Mitsuhiro Yoshioka.

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Tsutsui-Kimura, I., Ohmura, Y., Izumi, T. et al. Nicotine provokes impulsive-like action by stimulating α4β2 nicotinic acetylcholine receptors in the infralimbic, but not in the prelimbic cortex. Psychopharmacology 209, 351–359 (2010). https://doi.org/10.1007/s00213-010-1804-0

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