The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal.
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.
Jackson
K J
KJ
Department of Pharmacology and Toxicology, Medical Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA. jacksonkj@vcu.edu
McIntosh
J M
JM
Brunzell
D H
DH
Sanjakdar
S S
SS
Damaj
M I
MI
D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D020916:Conotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology
D002121:Calcium Channel Blockers; D020916:Conotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C104518:nicotinic receptor alpha6; D009538:Nicotine