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Jackson KJ, McIntosh JM, Brunzell DH, Sanjakdar SS, Damaj MI: The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal. Biochem Pharmacol. 2009 Oct 1;78(7):852-62. Epub 2009 Jul 3.
The alpha6 nicotinic acetylcholine receptor (nAChR) subunit is involved in nicotine-stimulated dopamine release in the striatum. It is expressed in brain regions and coexpressed with nAChR subtypes implicated in nicotine dependence behaviors; hence, this subunit may play a role in nicotine dependence. Using the alpha6-selective antagonist alpha-conotoxin H9A;L15A (MII [H9A;L15A]), we determined the role of alpha6* nAChRs in the pharmacological and behavioral effects of nicotine. We measured effects of pretreatment with MII [H9A;L15A] on analgesia, locomotion, and body temperature after a single injection of nicotine. Effects of MII [H9A;L15A] on nicotine reward were measured using the conditioned place preference (CPP) paradigm. We further measured physical (somatic signs and hyperalgesia) and affective [anxiety-related behavior and conditioned place aversion (CPA)] nicotine withdrawal behaviors after extended nicotine exposure. Results showed that MII [H9A;L15A] did not block acute nicotine effects on the behaviors measured. Conversely, MII [H9A:l15A] blocked the expression of nicotine CPP, as well as withdrawal-associated CPA and anxiety-related behavior in the elevated plus maze, but not withdrawal-induced somatic signs or hyperalgesia. These results suggest a role for the alpha6 nAChR subunit in nicotine reward and affective nicotine withdrawal but not acute nicotine-induced or physical withdrawal behaviors. |
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