Nicotine and extinction of fear conditioning
Open accessAbstract
Despite known health risks, nicotine use remains high, especially in populations diagnosed with mental illnesses, including anxiety disorders and Post-Traumatic Stress Disorder (PTSD). Smoking in these populations may relate to the effects of nicotine on emotional memories. The current study examined the effects of nicotine administration on the extinction of conditioned fear memories. C57BL/6J mice were trained with two white noise conditioned stimulus (CS; 30 s, 85 dB)-foot shock (2 s, 0.57 mA) pairings. Extinction sessions consisted of six presentations of the CS (60 s) across multiple days. Mice were either tested in an AAA design, in which all stages occurred in the same context, or in an ABA design to identify if context changes alter extinction. Saline or nicotine was administered 5 min before training and/or extinction. In the AAA design, nicotine administration before training did not alter extinction. Nicotine administered prior to extinction sessions enhanced extinction and nicotine administered before training and extinction decreased extinction. In the ABA design, nicotine administered before extinction enhanced extinction and blocked context renewal of conditioned fear, while nicotine administered during training and extinction did not alter extinction but enhanced the context renewal of conditioned fear. Nicotine has a differential effect on extinction of fear conditioning depending on when it is administered. Administration during extinction enhances extinction whereas administration during training and extinction may strengthen contextual fear memories and interfere with extinction.
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There is evidence that nicotine exposure precedes and exacerbates the effects of exposure to stress or trauma.
“However, there is evidence that nicotine exposure precedes and exacerbates the effects of exposure to stress or trauma (Elias et al., 2010).”
From Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke (2017) · cites this paper as Elias et al., 2010
Cigarette smoke exposure during stress has been shown to strengthen learned fear responses.
“CS exposure during stress has been shown to strengthen learned fear responses (Davis et al., 2006; Elias et al., 2010; Kutlu and Gould, 2015).”
From Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke (2017) · cites this paper as Elias et al., 2010
Acute nicotine administered during the extinction phase enhanced extinction and impaired renewal of cued fear memories.
“Elias et al. (2010) found that acute nicotine enhanced extinction and impaired renewal of cued fear memories when administered during the extinction phase”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Elias et al. (2010)
Nicotine administration during both training and extinction phases impaired extinction and enhanced renewal of cued fear.
“whereas nicotine administration during both training and extinction phases impaired extinction and enhanced renewal of cued fear.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Elias et al. (2010)
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Cites
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444 · see citing works
Neural Mechanisms of Extinction Learning and Retrieval
Quirk, G. J., & Mueller, D. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301555 · Cited by 1,645 · see citing works
Neuronal signalling of fear memory
Maren, S., & Quirk, G. J. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1535 · Cited by 1,428 · see citing works
The neuroanatomical and neurochemical basis of conditioned fear
Fendt, M., & Fanselow, M. S. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00016-0 · Cited by 1,092 · see citing works
Levin, E. D., McClernon, F. J., & Rezvani, A. H. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0164-7 · Cited by 820 · see citing works
Uncontrollability and unpredictability in post-traumatic stress disorder: An animal model.
Foa, E. B., Zinbarg, R., & Rothbaum, B. O. (1992) · Psychological Bulletin · doi:10.1037/0033-2909.112.2.218 · Cited by 787 · see citing works
Prefrontal mechanisms in extinction of conditioned fear
Quirk, G. J., Garcia, R., & González-Lima, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.010 · Cited by 682 · see citing works
Contextual and temporal modulation of extinction: behavioral and biological mechanisms
Bouton, M. E., Westbrook, R. F., Corcoran, K. A., & Maren, S. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.12.015 · Cited by 671 · see citing works
Breslau, N., Davis, G. C., & Schultz, L. R. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.3.289 · Cited by 573 · see citing works
Burgos-Robles, A., Vidal-Gonzalez, I., Santini, E., & Quirk, G. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.021 · Cited by 516 · see citing works
Hopper, J. W., Frewen, P. A., van der Kolk, B. A., & Lanius, R. A. (2007) · Journal of Traumatic Stress · doi:10.1002/jts.20284 · Cited by 376 · see citing works
Hippocampal involvement in contextual modulation of fear extinction
Ji, J., & Maren, S. (2007) · Hippocampus · doi:10.1002/hipo.20331 · Cited by 297 · 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
Mueller, D., Porter, J. T., & Quirk, G. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3248-07.2008 · Cited by 284 · see citing works
Psychiatric disorders and stages of smoking
Breslau, N., Novak, S. P., & Kessler, R. C. (2004) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00317-2 · Cited by 274 · see citing works
A retrieval cue for extinction attenuates spontaneous recovery.
Brooks, D. C., & Bouton, M. E. (1993) · Journal of Experimental Psychology Animal Behavior Processes · doi:10.1037/0097-7403.19.1.77 · Cited by 272 · see citing works
Post-traumatic stress disorder and smoking: A systematic review
Fu, S. S., McFall, M., Saxon, A. J., Beckham, J. C., Carmody, T. P., Baker, D. G., & Joseph, A. M. (2007) · Nicotine & Tobacco Research · doi:10.1080/14622200701488418 · Cited by 260 · see citing works
Modulation of Hippocampus-Dependent Learning and Synaptic Plasticity by Nicotine
Kenney, J. W., & Gould, T. J. (2008) · Molecular Neurobiology · doi:10.1007/s12035-008-8037-9 · Cited by 242 · see citing works
State-dependent fear extinction with two benzodiazepine tranquilizers.
Bouton, M. E., Kenney, F. A., & Rosengard, C. (1990) · Behavioral Neuroscience · doi:10.1037//0735-7044.104.1.44 · Cited by 212 · see citing works
Daily smoking and the subsequent onset of psychiatric disorders
Breslau, N., Novak, S. P., & Kessler, R. C. (2004) · Psychological Medicine · doi:10.1017/s0033291703008869 · Cited by 200 · see citing works
Koenen, K. C., Hitsman, B., Lyons, M. J., Niaura, R., McCaffery, J., Goldberg, J., Eisen, S. A., True, W., & Tsuang, M. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1258 · Cited by 197 · see citing works
State-dependent fear extinction with two benzodiazepine tranquilizers.
Bouton, M. E., Kenney, F. A., & Rosengard, C. (1990) · Behavioral Neuroscience · doi:10.1037/0735-7044.104.1.44 · Cited by 178 · see citing works
Nicotine enhancement of contextual fear conditioning
Gould, T. J., & Wehner, J. M. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(98)00157-0 · Cited by 151 · see citing works
Genetics of PTSD: fear conditioning as a model for future research
Amstadter, A. B., Nugent, N. R., & Koenen, K. C. (2009) · Psychiatric Annals · doi:10.3928/00485713-20090526-01 · Cited by 150 · see citing works
Withdrawal from Chronic Nicotine Administration Impairs Contextual Fear Conditioning in C57BL/6 Mice
Davis, J. A., James, J. R., Siegel, S. J., & Gould, T. J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2853-05.2005 · Cited by 146 · see citing works
Self-citationWoods, A. M., & Bouton, M. E. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.5.1159 · Cited by 133 · see citing works
Nicotine enhances contextual fear conditioning in C57BL/6J mice at 1 and 7 days post-training
Gould, T. J., & Stephen Higgins, J. (2003) · Neurobiology of Learning and Memory · doi:10.1016/s1074-7427(03)00057-1 · Cited by 123 · see citing works
Self-citationDavis, J. A., Kenney, J. W., & Gould, T. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3242-07.2007 · Cited by 107 · see citing works
Is posttraumatic stress disorder a stress‐induced fear circuitry disorder?
Shin, L. M., & Handwerger, K. (2009) · Journal of Traumatic Stress · doi:10.1002/jts.20442 · Cited by 102 · see citing works
The effect of yohimbine on the extinction of conditioned fear: A role for context.
Morris, R. W., & Bouton, M. E. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.3.501 · Cited by 100 · see citing works
Benowitz, N. L., Porchet, H. C., & Jacob, P. (1989) · Progress in brain research · doi:10.1016/s0079-6123(08)62487-5 · Cited by 98 · see citing works
Davis, J. A., & Gould, T. J. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0047-y · Cited by 78 · see citing works
Davis, J. A., & Gould, T. J. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0624-8 · Cited by 72 · see citing works
Self-citationOverview of Biological Themes in PTSDa
Pitman, R. K. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48264.x · Cited by 66 · see citing works
Nicotine enhances both foreground and background contextual fear conditioning
Davis, J. A., Porter, J., & Gould, T. J. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.10.026 · Cited by 65 · see citing works
Ad lib smoking in post-traumatic stress disorder: An electronic diary study
Beckham, J. C., Wiley, M. T., Miller, S., Dennis, M. F., Wilson, S. M., McClernon, F. J., & Calhoun, P. S. (2008) · Nicotine & Tobacco Research · doi:10.1080/14622200802123302 · Cited by 64 · see citing works
Animal Models of Relevance to PTSD
Rasmusson, A. M., & Charney, D. S. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48290.x · Cited by 61 · see citing works
Nicotine and Hippocampus-Dependent Learning: Implications for Addiction
Gould, T. J. (2006) · Molecular Neurobiology · doi:10.1385/mn:34:2:93 · Cited by 61 · see citing works
Gulick, D., & Gould, T. J. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0982-x · Cited by 49 · see citing works
Tian, S., Gao, J., Han, L., Fu, J., Li, C., & Li, Z. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.03.005 · Cited by 48 · see citing works
Nicotine enhances context learning but not context-shock associative learning.
Kenney, J. W., & Gould, T. J. (2008) · Behavioral Neuroscience · doi:10.1037/a0012807 · Cited by 45 · see citing works
Gould, T. J. (2003) · Integrative Psychological and Behavioral Science · doi:10.1007/bf02688830 · Cited by 44 · see citing works
Kenney, J. W., Florian, C., Portugal, G. S., Abel, T. G., & Gould, T. J. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.153 · Cited by 42 · see citing works
Gould, T. J., & Lewis, M. C. (2005) · Learning & Memory · doi:10.1101/lm.89105 · Cited by 33 · see citing works
Neumann, D. L., & Longbottom, P. L. (2008) · Behaviour Research and Therapy · doi:10.1016/j.brat.2007.12.004 · Cited by 32 · see citing works
Gulick, D., & Gould, T. J. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.45 · Cited by 23 · see citing works
Translating findings from basic fear research to clinical psychiatry in Puerto Rico.
Quirk, G. J., Martínez, K., & Nazario, L. L. (2007) · PubMed · Cited by 6 · see citing works
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Bruijnzeel, A. W. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.02.015 · Cited by 172 · see citing works
Sex differences in fear extinction
Velasco, E. R., Florido, A., Milad, M. R., & Andero, R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.020 · Cited by 125 · see citing works
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Kaplan, G. B., & Moore, K. (2011) · Pharmacology, Biochemistry and Behavior · doi:10.1016/j.pbb.2011.01.009 · Cited by 104 · see citing works
Nicotine modulation of fear memories and anxiety: Implications for learning and anxiety disorders
Kutlu, M. G., & Gould, T. J. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.07.029 · Cited by 97 · see citing works
Cholinergic regulation of fear learning and extinction
Wilson, M. A., & Fadel, J. R. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23840 · Cited by 98 · see citing works
Nabel, E. M., & Morishita, H. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00146 · Cited by 85 · see citing works
Besson, M., & Forget, B. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2016.00160 · Cited by 73 · see citing works
Nicotine addiction and psychiatric disorders
Kutlu, M. G., Parikh, V., & Gould, T. J. (2015) · International Review of Neurobiology · doi:10.1016/bs.irn.2015.08.004 · Cited by 65 · see citing works
Self-citationSubstance abuse, memory, and post-traumatic stress disorder
Tipps, M. E., Raybuck, J. D., & Lattal, K. M. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.12.002 · Cited by 62 · see citing works
New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine
Grizzell, J. A., & Echeverrı́a, V. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1359-2 · Cited by 61 · see citing works
de Souza, R. R., Robertson, N. M., Pruitt, D. T., Gonzales, P. A., Hays, S. A., Rennaker, R. L., Kilgard, M. P., & McIntyre, C. K. (2019) · Stress · doi:10.1080/10253890.2019.1602604 · Cited by 49 · see citing works
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Kutlu, M. G., & Gould, T. J. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.01.031 · Cited by 42 · see citing works
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Kutlu, M. G., & Gould, T. J. (2015) · Current topics in behavioral neurosciences · doi:10.1007/978-3-319-13665-3_6 · Cited by 41 · see citing works
Kim, J. H., Perry, C. J., Ganella, D. E., & Madsen, H. B. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.10.018 · Cited by 35 · see citing works
Cholinergic neurotransmission in the basolateral amygdala during cued fear extinction
Kellis, D. M., Kaigler, K. F., Witherspoon, E., Fadel, J. R., & Wilson, M. A. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100279 · Cited by 28 · see citing works
Chandler, L. J., Vaughan, D. T., & Gass, J. T. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.837657 · Cited by 24 · see citing works
Smiley, C. E., McGonigal, J. T., Valvano, T., Newsom, R. J., Otero, N. K. H., & Gass, J. T. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05622-9 · Cited by 19 · see citing works
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Cambiaghi, M., Grosso, A., Renna, A., Concina, G., & Sacchetti, B. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.036 · Cited by 11 · see citing works
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Palmisano, A. N., Hudd, E. C., McQuade, C., de Wit, H., & Astur, R. S. (2017) · Addictive Behaviors · doi:10.1016/j.addbeh.2017.09.008 · Cited by 12 · see citing works
Rodrigues, J. V. F., Vidigal, A. P. P., Minassa, V. S., Batista, T. J., de Lima, R. M. S., Funck, V. R., Antero, L. S., Resstel, L. B. M., Coitinho, J. B., Bertoglio, L. J., et al. (2020) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2020.106929 · Cited by 8 · see citing works
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Pittenger, S. T. (2016) · Lincoln (University of Nebraska) · Cited by 1 · see citing works
Ramírez, D. A., Ortega, L. A., Fundación Universitaria Konrad Lorenz, B., & Fundación Universitaria Konrad Lorenz, B. (2021) · Suma Psicológica · doi:10.14349/sumapsi.2021.v28.n1.5 · Cited by 1 · see citing works
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- Authors
- Elias, G. A., Gulick, D., Wilkinson, D. S., & Gould, T. J.
- Affiliations
- Temple University (US)
- Corresponding author
- Gould, T.J.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 165
- Issue
- 4
- Pages
- 1063-1073
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2814978
- OpenAlex
- W2019113229
- Cited by
- 36
- References
- 46
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute for Drug Abuse (NIDA) (DA017949)
- NIDA diversity supplement (DA024787-01A1S1)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine, fear extinction, fear conditioning, contextual fear memory, anxiety disorders, post-traumatic stress disorder, emotional memory
- MeSH terms
- Acoustic Stimulation, Animals, Conditioning, Classical, Electroshock, Extinction, Psychological, Fear, Female, Male, Mice, Inbred C57BL, Nicotine, Random Allocation, Time Factors, Nicotinic Agonists, Mice
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