Effects of nicotine and stress exposure across generations in C57BL/6 mice
Open accessAbstract
Chronic administration of nicotine or exposure to stress can produce long-lasting behavioral and physiological changes in humans and animals alike. Further, the impact of nicotine and stress exposure can be inherited by offspring to produce persistent changes in physiology and behavior. To determine if nicotine and stress interact across generations to influence offspring behavior we exposed F0 male mice to nicotine and F1 male and female mice to chronic unpredictable stress during adolescence. We then measured locomotor sensitization to repeated nicotine injections in the subsequent F2 and F3 generations. Stress exposure alone (F1) did not influence locomotor sensitization in any lineage. However, in the F1 male lineage, F0 nicotine exposure abrogated locomotor sensitization in F2 male and transiently enhanced locomotor sensitization in F2 female offspring. These effects were not passed down to the F3 generations or observed in the F1 female lineage. F1 stress exposure modulated the effects of prior F0 nicotine exposure in a sex-dependent manner. Specifically, stress blunted the nicotine-induced enhancement in locomotor sensitization observed in F2 female offspring of F1 males. The effect of F0 nicotine and F1 stress exposure in females appears to have skipped a generation and enhanced nicotine sensitization only in the F3 generation, and only in females. This novel multigenerational exposure paradigm examining the inheritance of two different environmental exposures demonstrates that nicotine responses can be modified by nicotine and stress exposure from previous generations, and these effects are strongly influenced by sex.
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Cites
The neural basis of drug craving: An incentive-sensitization theory of addiction
Robinson, T. (1993) · Brain Research Reviews · doi:10.1016/0165-0173(93)90013-p · Cited by 7,346 · see citing works
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340 · see citing works
McEwen, B. S. (1993) · Archives of Internal Medicine · doi:10.1001/archinte.153.18.2093 · Cited by 4,365 · see citing works
Procedures for Detecting Outlying Observations in Samples
Grubbs, F. E. (1969) · Technometrics · doi:10.1080/00401706.1969.10490657 · Cited by 4,105 · see citing works
Current Cigarette Smoking Among Adults — United States, 2016
Jamal, A., Phillips, E., Gentzke, A. S., Homa, D. M., Babb, S. D., King, B. A., & Neff, L. J. (2018) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6702a1 · Cited by 3,060 · see citing works
Current Cigarette Smoking Among Adults — United States, 2005–2014
Jamal, A., Homa, D. M., O’Connor, E., Babb, S. D., Caraballo, R. S., Singh, T., Hu, S., & King, B. A. (2015) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6444a2 · Cited by 2,544 · see citing works
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring
Ng, S.-F., Lin, R. C. Y., Laybutt, D. R., Barres, R., Owens, J. A., & Morris, M. J. (2010) · Nature · doi:10.1038/nature09491 · Cited by 1,327 · see citing works
Epigenetic transmission of the impact of early stress across generations
Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., Vizi, S., & Mansuy, I. M. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.036 · Cited by 1,125 · see citing works
Kaati, G., Bygren, L., & Edvinsson, S. (2002) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200859 · Cited by 896 · see citing works
Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S., & Bale, T. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0914-13.2013 · Cited by 814 · see citing works
Tobacco Use Among Middle and High School Students—United States, 1999
(2000) · JAMA · doi:10.1001/jama.283.9.1134-jwr0301-2-1 · Cited by 787 · see citing works
Current Cigarette Smoking Among Adults—United States, 2011
Agaku, I. T., King, B. A., & Dube, S. R. (2013) · JAMA · doi:10.1001/jama.2012.114523 · Cited by 773 · see citing works
Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization
Tapper, A. R., McKinney, S. L., Nashmi, R., Schwarz, J., Deshpande, P., Labarca, C., Whiteaker, P., Marks, M. J., Collins, A. C., & Lester, H. A. (2004) · Science · doi:10.1126/science.1099420 · Cited by 686 · see citing works
Lane, N., Dean, W., Erhardt, S., Hajkova, P., Surani, A., Walter, J., & Reik, W. (2003) · genesis · doi:10.1002/gene.10168 · Cited by 667 · see citing works
Meta-analysis of the acute effects of nicotine and smoking on human performance
Heishman, S. J., Kleykamp, B. A., & Singleton, E. G. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1848-1 · Cited by 651 · see citing works
(2015) · PubMed · Cited by 615 · see citing works
<scp>N</scp> icotine and the adolescent brain
Yuan, M., Cross, S. J., Loughlin, S. E., & Leslie, F. M. (2015) · The Journal of Physiology · doi:10.1113/jp270492 · Cited by 582 · see citing works
The maternal and fetal physiologic effects of nicotine
Lambers, D. S., & Clark, K. E. (1996) · Seminars in Perinatology · doi:10.1016/s0146-0005(96)80079-6 · Cited by 577 · see citing works
Effect of nicotine and nicotinic receptors on anxiety and depression
Picciotto, M. R., Brunzell, D. H., & Caldarone, B. J. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00006 · Cited by 483 · see citing works
Epigenetic inheritance of a cocaine-resistance phenotype
Vassoler, F. M., White, S., Schmidt, H. D., Sadri‐Vakili, G., & Pierce, R. C. (2012) · Nature Neuroscience · doi:10.1038/nn.3280 · Cited by 419 · see citing works
Epigenetics and the origins of paternal effects
Curley, J. P., Rahia Mashoodh, A., & Champagne, F. A. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.06.018 · Cited by 415 · see citing works
Electronic Cigarette Use Among Adults: United States, 2014.
Schoenborn, C. A., & Gindi, R. M. (2015) · PubMed · Cited by 372 · see citing works
Studying both sexes: a guiding principle for biomedicine
Clayton, J. A. (2016) · The FASEB Journal · doi:10.1096/fj.15-279554 · Cited by 358 · see citing works
Paternal Transmission of Stress-Induced Pathologies
Dietz, D. M., LaPlant, Q., Watts, E. L., Hodes, G. E., Russo, S. J., Feng, J., Oosting, R. S., Vialou, V., & Nestler, E. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.05.005 · Cited by 346 · see citing works
Vulnerability to Posttraumatic Stress Disorder in Adult Offspring of Holocaust Survivors
Yehuda, R., Schmeidler, J., Wainberg, M., Binder-Brynes, K., & Duvdevani, T. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.9.1163 · Cited by 327 · see citing works
Nicotine delivery kinetics and abuse liability.
Henningfield, J. E., & Keenan, R. M. (1993) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.61.5.743 · Cited by 292 · see citing works
Levine, A., Huang, Y., Drisaldi, B., Griffin, E. A., Pollak, D. D., Xu, S., Yin, D., Schaffran, C., Kandel, D. B., & Kandel, E. R. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003062 · Cited by 280 · see citing works
Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine
Mereu, G., Yoon, K.-W. P., Boi, V., Gessa, G. L., Naes, L., & Westfall, T. C. (1987) · European Journal of Pharmacology · doi:10.1016/0014-2999(87)90556-5 · Cited by 271 · see citing works
Chronic Social Instability Induces Anxiety and Defective Social Interactions Across Generations
Saavedra-Rodríguez, L., & Feig, L. A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.035 · Cited by 270 · see citing works
Govorko, D., Bekdash, R. A., Zhang, C., & Sarkar, D. K. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.006 · Cited by 244 · see citing works
Robinson, T. G. (1998) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(97)00020-1 · Cited by 230 · see citing works
Mill, J., & Petronis, A. (2008) · Journal of Child Psychology and Psychiatry and Allied Disciplines · doi:10.1111/j.1469-7610.2008.01909.x · Cited by 228 · see citing works
Environmental stress and epigenetic transgenerational inheritance
Skinner, M. K. (2014) · BMC Medicine · doi:10.1186/s12916-014-0153-y · Cited by 225 · see citing works
Staley, J. K., Krishnan-Sarin, S., Cosgrove, K. P., Krantzler, E., Frohlich, E., Perry, E., Dubin, J. A., Estok, K., Brenner, E., Baldwin, R. M., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0546-06.2006 · Cited by 223 · cited 1× · see citing works
“In addition, this dose upregulates nicotinic acetylcholine receptors in the brain of rodents (Yohn, Turner, & Blendy, 2014), a hallmark of chronic NIC use in humans (Staley, 2006).”
BackgroundCharacterization 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
Szutorisz, H., DiNieri, J. A., Sweet, E. S., Egervári, G., Michaelides, M., Carter, J. M., Ren, Y., Miller, M. L., Blitzer, R. D., & Hurd, Y. L. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.352 · Cited by 197 · see citing works
Plasma nicotine levels after smoking cigarettes with high, medium, and low nicotine yields.
Russell, M. A., Wilson, C. M., Patel, U. A., Feyerabend, C., & Cole, P. V. (1975) · BMJ · doi:10.1136/bmj.2.5968.414 · Cited by 192 · see citing works
Perinatal nicotine exposure induces asthma in second generation offspring
Rehan, V. K., Liu, J., Naeem, E., Tian, J., Sakurai, R., Kwong, K., Akbari, O., & Torday, J. S. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-129 · Cited by 175 · see citing works
Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens
Damsma, G., Day, J. C., & Fibiger, H. C. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90798-x · Cited by 169 · see citing works
Male-line transgenerational responses in humans
Pembrey, M. E. (2010) · Human Fertility · doi:10.3109/14647273.2010.524721 · Cited by 164 · see citing works
Yohn, N. L., Bartolomei, M. S., & Blendy, J. A. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.03.002 · Cited by 142 · see citing works
Self-citationBenwell, M. E. M., & Balfour, D. J. K. (1979) · Psychopharmacology · doi:10.1007/bf00426913 · Cited by 132 · see citing works
Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers.
Benowitz, N. L., & Sharp, D. S. (1989) · Circulation · doi:10.1161/01.cir.80.5.1309 · Cited by 131 · see citing works
Finegersh, A., & Homanics, G. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099078 · Cited by 129 · see citing works
Epigenetics of drug abuse: predisposition or response
Nielsen, D. A., Utrankar, A., Reyes, J. A., Simons, D. D., & Kosten, T. R. (2012) · Pharmacogenomics · doi:10.2217/pgs.12.94 · Cited by 125 · see citing works
National Center for Health Statistics
Keller, K. (2008) · Encyclopedia of Obesity · doi:10.4135/9781412963862.n310 · Cited by 119 · see citing works
McCormick, C. M., Robarts, D., Gleason, E., & Kelsey, J. E. (2004) · Hormones and Behavior · doi:10.1016/j.yhbeh.2004.05.004 · Cited by 105 · see citing works
Stress and the Individual: Mechanisms Leading to Disease
McEwen, B. S. (1993) · Archives of Internal Medicine · doi:10.1001/archinte.1993.00410180039004 · Cited by 103 · see citing works
Sensitization to nicotine: How the animal literature might inform future human research
DiFranza, J. R., & Wellman, R. J. (2007) · Nicotine & Tobacco Research · doi:10.1080/14622200601078277 · Cited by 91 · see citing works
Transgenerational Transmission of Hyperactivity in a Mouse Model of ADHD
Zhu, J., Lee, K. P., Spencer, T. J., Biederman, J., & Bhide, P. G. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4402-13.2014 · Cited by 90 · see citing works
Yohn, N. L., & Blendy, J. A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.11 · Cited by 87 · see citing works
Self-citationMultigenerational effects of adolescent morphine exposure on dopamine D2 receptor function
BYRNES, J. J., Johnson, N. L., Carini, L. M., et al. (2013) · Psychopharmacology · doi:10.1007/s00213-012-2960-1 · Cited by 81 · see citing works
Turner, J. R., Castellano, L. M., & Blendy, J. A. (2011) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntq206 · Cited by 78 · see citing works
Self-citationGlobal DNA methylation is influenced by smoking behaviour
Hillemacher, T., Frieling, H., Moskau, S., Muschler, M. A. N., Semmler, A., Kornhuber, J., Klockgether, T., Bleich, S., & Linnebank, M. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2007.12.005 · Cited by 75 · see citing works
Jordanov, J. S. (1990) · European Journal of Pediatrics · doi:10.1007/bf01959534 · Cited by 67 · see citing works
A test battery for measuring nicotine effects in mice
Marks, M. J., Romm, E., Bealer, S. M., & Collins, A. C. (1985) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(85)90577-5 · Cited by 65 · see citing works
Sex differences in brain and behavior: emphasis on nicotine, nitric oxide and place learning
Pöğün, Ş. (2001) · International Journal of Psychophysiology · doi:10.1016/s0167-8760(01)00168-4 · Cited by 63 · see citing works
Transgenerational effects of fetal and neonatal exposure to nicotine
Holloway, A. C., Cuu, D. Q., Morrison, K. M., Gerstein, H. C., & Tarnopolsky, M. A. (2007) · Endocrine · doi:10.1007/s12020-007-0043-6 · Cited by 61 · see citing works
Todtenkopf, M. S., Mihalakopoulos, A., & Stellar, J. R. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00272-5 · Cited by 59 · see citing works
Dai, J., Wang, Z., Xu, W., Zhang, M., Zhu, Z., Zhao, X., Zhang, D., Nie, D., Wang, L., & Qiao, Z. (2017) · Scientific Reports · doi:10.1038/s41598-017-07920-3 · Cited by 58 · see citing works
Decreased anxiety-like behavior in beta3 nicotinic receptor subunit knockout mice
Booker, T. K., Butt, C. M., Wehner, J. M., Heinemann, S. F., & Collins, A. C. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.04.011 · Cited by 49 · see citing works
Novel Insights on the Effect of Nicotine in a Murine Colitis Model
AlSharari, S. D., Akbarali, H. I., Abdullah, R. A., Shahab, O., Auttachoat, W., Ferreira, G. A., White, K. L., Lichtman, A. H., Cabral, G. A., & Damaj, M. I. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.198796 · Cited by 46 · see citing works
Intergenerational genomic DNA methylation patterns in mouse hybrid strains
Orozco, L. D., Rubbi, L., Martin, L. J., Fang, F., Hormozdiari, F., Che, N., Smith, A. D., Lusis, A. J., & Pellegrini, M. A. (2014) · Genome biology · doi:10.1186/gb-2014-15-5-r68 · Cited by 39 · see citing works
The Inverse Relationship between Tobacco Use and Body Weight
Grunberg, N. E. (1990) · Springer eBooks · doi:10.1007/978-1-4899-1669-3_9 · Cited by 29 · see citing works
Yohn, N. L., Turner, J. R., & Blendy, J. A. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.211706 · Cited by 28 · see citing works
Self-citationCaruso, M. J., Reiss, D. E., Caulfield, J. I., Thomas, J. L., Baker, A. N., Cavigelli, S. A., & Kamens, H. M. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.08.001 · Cited by 23 · see citing works
Self-citation
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Research works printed but not linked: 1
- Substance Abuse and Mental Health Services Administration (SAMHSA). (2011). Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. Substance Abuse, (HHS Publication No. (SMA) 11–4658), 1– 143. https://doi.org/NSDUH Series H-41, HHS Publication No. (SMA) 11–4658
Cited by
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Nicotine on the developing brain.
Castro, E. M., Lotfipour, S., & Leslie, F. M. (2023) · Pharmacological research · doi:10.1016/j.phrs.2023.106716 · Cited by 140 · see citing works
- Authors
- Yohn, N. L., Caruso, M. J., & Blendy, J. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Blendy, Julie A.
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2018-11-20
- Volume
- 22
- Issue
- 1
- Pages
- 142-150
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- PMC
- PMC6453752
- OpenAlex
- W2901621178
- Cited by
- 13
- References
- 66
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 3
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Drug Abuse (DA033646, T32DA28874)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, chronic unpredictable mild stress, transgenerational inheritance, locomotor sensitization, sex differences, multigenerational exposure, C57BL/6 mice, nicotine sensitization, environmental epigenetics
- MeSH terms
- Animals, Female, Male, Mice, Inbred C57BL, Nicotine, Pregnancy, Prenatal Exposure Delayed Effects, Random Allocation, Stress, Psychological, Mice
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