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Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

Content Provider	Springer Nature Link
Author	Higa, K. K . Grim, A. Kamenski, M. E. Enkhuizen, J. Zhou, X. Li, K. Naviaux, J. C. Wang, L. Naviaux, R. K. Geyer, M. A. Markou, A. Young, J. W.
Copyright Year	2017
Abstract	Smoking is the leading cause of preventable death in the USA, but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts.We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the five-choice continuous performance test (5C-CPT).Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg kg−1 day−1 nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg kg−1 day−1 nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were killed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal.Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits.The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts.
Starting Page	1573
Ending Page	1586
Page Count	14
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	234
Issue Number	9-10
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-02-28
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Response inhibition α7 Nicotinic acetylcholine receptor Five-choice continuous performance task Attention mGluR5 Dopamine D4 receptor Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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