Contributions of [beta]2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice

• Published in: Psychopharmacology 2015-04, Vol.232 (7), p.1207
• Main Authors: Cole, Robert D, Poole, Rachel L, Guzman, Dawn M, Gould, Thomas J, Parikh, Vinay
• Format: Article
• Language: English
• Subjects: Drug addiction; Nicotine; Psychopharmacology; Rodents
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-014-3754-4

Deficits in executive functions underlie compulsive drug use, and understanding how nicotine influences these cognitive processes may provide important information on neurobiological substrates of nicotine addiction. Accumulating evidence suggests that [beta]2 subunit-containing nicotinic receptors (nAChRs) are involved in the reinforcing process of nicotine addiction. Whether these nAChRs also contributes to the detrimental effects of chronic nicotine on flexible decision-making is not known. In the present study, the effects of chronic nicotine were assessed in mice with partial or complete deletion of the [beta]2 subunit-containing nAChR gene ([beta]2+/- or [beta]2-/-) performing an operant cognitive flexibility task. Visual discrimination learning was not affected in saline-treated [beta]2 nAChR mutants as compared to the wild-type ([beta]2+/+) mice; yet, chronic nicotine facilitated acquisition of visual discrimination in all genotypes. The acquisition of new egocentric response strategy set-shifting remained similar in all genotypes, and there was no effect of treatment. Chronic nicotine treatment impaired reversal learning in [beta]2+/+ mice by increasing response perseveration to the previously rewarded stimulus. Moreover, the acquisition of inverted stimulus-reward contingencies did not differ between [beta]2+/+ and [beta]2-/- mice exposed to chronic nicotine. Interestingly, nicotine-induced reversal learning deficits were not observed in [beta]2+/- mice. Collectively, these findings suggest that [beta]2 subunit-containing nAChRs are not critical for visual discrimination learning and extra dimensional rule shift. However, sustained activation of these nAChRs with nicotine may interfere with inhibitory control processes influencing affective shifts in stimulus-reward contingencies.