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Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse
Author(s) -
Slater Cassandra A.,
Jackson Asti,
Muldoon Pretal P.,
Dawson Anton,
O'Brien Megan,
Soll Lindsey G.,
Abdullah Rehab,
Carroll F. Ivy,
Tapper Andrew R.,
Miles Michael F.,
Banks Matthew L.,
Bettinger Jill C.,
Damaj Imad M.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12918
Subject(s) - nicotine , mecamylamine , pharmacology , nicotinic agonist , varenicline , nicotinic acetylcholine receptor , righting reflex , hypothermia , chemistry , medicine , anesthesia , receptor , reflex
Background Ethanol (EtOH) and nicotine abuse are 2 leading causes of preventable mortality in the world, but little is known about the pharmacological mechanisms mediating co‐abuse. Few studies have examined the interaction of the acute effects of EtOH and nicotine. Here, we examine the effects of nicotine administration on the duration of EtOH‐induced loss of righting reflex (LORR) and characterize the nature of their pharmacological interactions in C57BL/6J mice. Methods We assessed the effects of EtOH and nicotine and the nature of their interaction in the LORR test using isobolographic analysis after acute injection in C57BL/6J male mice. Next, we examined the importance of receptor efficacy using nicotinic partial agonists varenicline and sazetidine. We evaluated the involvement of major nicotinic acetylcholine receptor (nAChR) subtypes using nicotinic antagonist mecamylamine and nicotinic α4‐ and α7‐knockout mice. The selectivity of nicotine's actions on EtOH‐induced LORR was examined by testing nicotine's effects on the hypnotic properties of ketamine and pentobarbital. We also assessed the development of tolerance after repeated nicotine exposure. Last, we assessed whether the effects of nicotine on EtOH‐induced LORR extend to hypothermia and EtOH intake in the drinking in the dark (DID) paradigm. Results We found that acute nicotine injection enhances EtOH's hypnotic effects in a synergistic manner and that receptor efficacy plays an important role in this interaction. Furthermore, tolerance developed to the enhancement of EtOH's hypnotic effects by nicotine after repeated exposure of the drug. α4* and α7 nAChRs seem to play an important role in nicotine–EtOH interaction in the LORR test. In addition, the magnitude of EtOH‐induced LORR enhancement by nicotine was more pronounced in C57BL/6J than DBA/2J mice. Furthermore, acute nicotine enhanced ketamine and pentobarbital hypnotic effects in the mouse. Finally, nicotine enhanced EtOH‐induced hypothermia but decreased EtOH intake in the DID test. Conclusions Our results demonstrate that nicotine synergistically enhances EtOH‐induced LORR in the mouse.