The role of various nicotinic receptor subunits and factors influencing nicotine conditioned place aversion
Open accessAbstract
Affective nicotine withdrawal symptoms are of major motivational significance in contributing to relapse and continued tobacco use; thus, it is important to understand the molecular and receptor-mediated mechanisms that mediate affective withdrawal behaviors. Previous work using the conditioned place aversion (CPA) model has shown that nicotine withdrawal is associated with a negative affective state, and place aversion to previously neutral environmental stimuli represents a motivational component in the maintenance of drug use. Thus, the purpose of this study was to evaluate the role of genotype, sex, and age and to extend previous studies examining the role of various nicotinic receptor subtypes in the development of nicotine withdrawal aversion using the CPA model. Mice were chronically treated with nicotine and conditioned for two days with various nicotinic receptor antagonists. The major findings showed that mecamylamine and dihydro-beta-erythroidine (DHbetaE), but not hexamethonium or methyllycaconitine citrate (MLA), precipitated significant aversion in the CPA model. This pharmacological data support our previous knockout mouse data suggesting that nicotine CPA is mediated by central beta2-containing nicotinic receptors, but not alpha7 nicotinic receptors. Further, we show that sex and age are contributing factors to the development of nicotine CPA. Overall, the results of our study provide some insight into pharmacological and behavioral factors involved in the development of an aversive motivational component associated with nicotine withdrawal.
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β2-containing and α6-containing nAChRs are necessary for conditioned place aversion, but α5 and α7 do not affect it.
“Pharmacological studies in nAChR null mice indicate that β2-containing and α6-containing nAChRs are necessary for CPA, but neither the α5, nor the α7 subunits affect CPA behavior [170, 172, 189].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [189]
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Cites
Characterization of spontaneous and precipitated nicotine withdrawal in the mouse
Damaj, M. I., Kao, W., & Martin, B. R. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.054908 · Cited by 222 · see citing works
Self-citationAge-dependent differences in nicotine reward and withdrawal in female mice
Kota, D., Martin, B. R., & Damaj, M. I. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1117-8 · Cited by 72 · cited 1× · see citing works
“Prior evaluations of female mice in nicotine withdrawal revealed that female mice did not express an anxiety-related response, suggesting that female mice are less sensitive to affective nicotine withdrawal (Kota et al., 2008).”
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Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
“In the conditioned place-aversion paradigm, the animal learns to avoid the compartment in which nicotine withdrawal is experienced (Jackson et al. 2009, Kenny & Markou 2001).”
BackgroundJackson, K. J., Sanjakdar, S. S., Muldoon, P. P., McIntosh, J. M., & Damaj, M. I. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.01.017 · Cited by 69 · see citing works
Self-citationMechanistic insights into nicotine withdrawal
Paolini, M., & De Biasi, M. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.07.075 · Cited by 66 · see citing works
- Authors
- Jackson, K. J., Kota, D. H., Martin, B. R., & Damaj, M. I.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Jackson, K.J.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 56
- Issue
- 6-7
- Pages
- 970-974
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3821837
- OpenAlex
- W2012738237
- Cited by
- 33
- References
- 2
- Citations by year
- 2025: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA012610, DA 05274, DA-12610, P50DA005274)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine withdrawal, conditioned place aversion, nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, mecamylamine, dihydro-beta-erythroidine, hexamethonium, methyllycaconitine, sex differences, age effects, genotypes, negative affect
- MeSH terms
- Age Factors, Animals, Avoidance Learning, Conditioning, Psychological, Female, Male, Nicotine, Receptors, Nicotinic, Sex Factors, Species Specificity, Substance Withdrawal Syndrome, Nicotinic Antagonists, Protein Subunits, Mice
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