Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse

Cassandra A. Slater; Asti Jackson; Pretal P. Muldoon; Anton Dawson; Megan O'Brien; Lindsey G. Soll; Rehab Abdullah; F. Ivy Carroll; Andrew R. Tapper; Michael F. Miles; Matthew L. Banks; Jill C. Bettinger; Imad M. Damaj

doi:10.1111/acer.12918

Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse

Cassandra A. Slater, Asti Jackson, Pretal P. Muldoon, Anton Dawson, Megan O'Brien, Lindsey G. Soll, Rehab Abdullah, F. Ivy Carroll, Andrew R. Tapper, Michael F. Miles, Matthew L. Banks, Jill C. Bettinger, Imad M. Damaj

Pharmacology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	62-72
Number of pages	11
Journal	Alcoholism: Clinical and Experimental Research
Volume	40
Issue number	1
DOIs	https://doi.org/10.1111/acer.12918
State	Published - Jan 1 2016

Bibliographical note

Funding Information:
The authors would like to thank Tie Shan-Han for technical assistance. This work was supported by National Institutes of Health grants DA-DA032246 and P50AA022537. All authors report no conflict of interest.

Publisher Copyright:
© 2016 Research Society on Alcoholism.

Keywords

Ethanol
Loss of Righting Reflex
Mice
Nicotine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/acer.12918

http://europepmc.org/articles/pmc4700556

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Slater, C. A., Jackson, A., Muldoon, P. P., Dawson, A., O'Brien, M., Soll, L. G., Abdullah, R., Carroll, F. I., Tapper, A. R., Miles, M. F., Banks, M. L., Bettinger, J. C., & Damaj, I. M. (2016). Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse. Alcoholism: Clinical and Experimental Research, 40(1), 62-72. https://doi.org/10.1111/acer.12918

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title = "Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse",

abstract = "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.",

keywords = "Ethanol, Loss of Righting Reflex, Mice, Nicotine",

author = "Slater, {Cassandra A.} and Asti Jackson and Muldoon, {Pretal P.} and Anton Dawson and Megan O'Brien and Soll, {Lindsey G.} and Rehab Abdullah and Carroll, {F. Ivy} and Tapper, {Andrew R.} and Miles, {Michael F.} and Banks, {Matthew L.} and Bettinger, {Jill C.} and Damaj, {Imad M.}",

note = "Funding Information: The authors would like to thank Tie Shan-Han for technical assistance. This work was supported by National Institutes of Health grants DA-DA032246 and P50AA022537. All authors report no conflict of interest. Publisher Copyright: {\textcopyright} 2016 Research Society on Alcoholism.",

year = "2016",

month = jan,

day = "1",

doi = "10.1111/acer.12918",

language = "English (US)",

volume = "40",

pages = "62--72",

journal = "Alcoholism: Clinical and Experimental Research",

issn = "0145-6008",

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TY - JOUR

T1 - Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse

AU - Slater, Cassandra A.

AU - Jackson, Asti

AU - Muldoon, Pretal P.

AU - Dawson, Anton

AU - O'Brien, Megan

AU - Soll, Lindsey G.

AU - Abdullah, Rehab

AU - Carroll, F. Ivy

AU - Tapper, Andrew R.

AU - Miles, Michael F.

AU - Banks, Matthew L.

AU - Bettinger, Jill C.

AU - Damaj, Imad M.

N1 - Funding Information: The authors would like to thank Tie Shan-Han for technical assistance. This work was supported by National Institutes of Health grants DA-DA032246 and P50AA022537. All authors report no conflict of interest. Publisher Copyright: © 2016 Research Society on Alcoholism.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Ethanol

KW - Loss of Righting Reflex

KW - Mice

KW - Nicotine

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Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse

Abstract

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Keywords

UN SDGs

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