Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

Stefania Tolu; Fabio Marti; Carole Morel; Carole Perrier; Nicolas Torquet; Stephanie Pons; Renaud de Beaurepaire; Philippe Faure

doi:10.1038/srep45116

journal article Open Access Mar 23, 2017

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

Stefania Tolu Fabio Marti

Carole Morel Carole Perrier Nicolas Torquet Stephanie Pons Renaud de Beaurepaire Philippe Faure

Scientific Reports Vol. 7 No. 1 · Springer Science and Business Media LLC

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Abstract

AbstractAlcohol and nicotine are the most widely co-abused drugs. Both modify the activity of dopaminergic (DA) neurons of the Ventral Tegmental Area (VTA) and lead to an increase in DA release in the Nucleus Accumbens, thereby affecting the reward system. Evidences support the hypothesis that distinct nicotinic acetylcholine receptors (nAChRs), the molecular target of acetylcholine (ACh) and exogenous nicotine, are also in addition implicated in the response to alcohol. The precise molecular and neuronal substrates of this interaction are however not well understood. Here we used in vivo electrophysiology in the VTA to characterise acute and chronic interactions between nicotine and alcohol. Simultaneous injections of the two drugs enhanced their responses on VTA DA neuron firing and chronic exposure to nicotine increased alcohol-induced DA responses and alcohol intake. Then, we assessed the role of β4 * nAChRs, but not β2 * nAChRs, in mediating acute responses to alcohol using nAChR subtypes knockout mice (β2−/− and β4−/− mice). Finally, we showed that nicotine-induced modifications of alcohol responses were absent in β2−/− and β4−/− mice, suggesting that nicotine triggers β2* and β4 * nAChR-dependent neuroadaptations that subsequently modify the responses to alcohol and thus indicating these receptors as key mediators in the complex interactions between these two drugs.

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References

55

[1]

Dani, J. A. & Harris, R. A. Nicotine addiction and comorbidity with alcohol abuse and mental illness. Nat Neurosci 8, 1465–1470 (2005). 10.1038/nn1580

[2]

Hendrickson, L. M., Guildford, M. J. & Tapper, A. R. Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence. Front Psychiatry 4, 29 (2013). 10.3389/fpsyt.2013.00029

[3]

Falk, D. E., Yi, H.-Y. & Hiller-Sturmhöfel, S. An epidemiologic analysis of co-occurring alcohol and tobacco use and disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol Res Health 29, 162–171 (2006).

[4]

DiFranza, J. R. & Guerrera, M. P. Alcoholism and smoking. J. Stud. Alcohol 51, 130–135 (1990). 10.15288/jsa.1990.51.130

[5]

Bobo, J. K. & Husten, C. Sociocultural influences on smoking and drinking. Alcohol Res Health 24, 225–232 (2000).

[6]

Schlaepfer, I. R., Hoft, N. R. & Ehringer, M. A. The genetic components of alcohol and nicotine co-addiction: from genes to behavior. Curr Drug Abuse Rev 1, 124–134 (2008). 10.2174/1874473710801020124

[7]

Doyon, W. M., Thomas, A. M., Ostroumov, A., Dong, Y. & Dani, J. A. Potential substrates for nicotine and alcohol interactions: a focus on the mesocorticolimbic dopamine system. Biochemical Pharmacology 86, 1181–1193 (2013). 10.1016/j.bcp.2013.07.007

[8]

Di Chiara, G. & Imperato, A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl. Acad. Sci. USA 85, 5274–5278 (1988). 10.1073/pnas.85.14.5274

[9]

Mameli-Engvall, M. et al. Hierarchical Control of Dopamine Neuron-Firing Patterns by Nicotinic Receptors. Neuron 50, 911–921 (2006). 10.1016/j.neuron.2006.05.007

[10]

Gessa, G. L., Muntoni, F., Collu, M., Vargiu, L. & Mereu, G. Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res. 348, 201–203 (1985). 10.1016/0006-8993(85)90381-6

[11]

Narahashi, T., Aistrup, G. L., Marszalec, W. & Nagata, K. Neuronal nicotinic acetylcholine receptors: a new target site of ethanol. Neurochem. Int. 35, 131–141 (1999). 10.1016/s0197-0186(99)00055-8

[12]

Lê, A. D., Corrigall, W. A., Harding, J. W., Juzytsch, W. & Li, T. K. Involvement of nicotinic receptors in alcohol self-administration. Alcoholism: Clinical and Experimental Research 24, 155–163 (2000). 10.1111/j.1530-0277.2000.tb04585.x

[13]

Liu, L. et al. Nicotinic acetylcholine receptors containing the α4 subunit modulate alcohol reward. Biol. Psychiatry 73, 738–746 (2013). 10.1016/j.biopsych.2012.09.019

[14]

Liu, L., Zhao-Shea, R., McIntosh, J. M. & Tapper, A. R. Nicotinic acetylcholine receptors containing the α6 subunit contribute to ethanol activation of ventral tegmental area dopaminergic neurons. Biochemical Pharmacology 86, 1194–1200 (2013). 10.1016/j.bcp.2013.06.015

[15]

Hendrickson, L. M., Zhao-Shea, R. & Tapper, A. R. Modulation of ethanol drinking-in-the-dark by mecamylamine and nicotinic acetylcholine receptor agonists in C57BL/6J mice. Psychopharmacology 204, 563–572 (2009). 10.1007/s00213-009-1488-5

[16]

Allosteric Receptors after 30 Years

Jean-Pierre Changeux, Stuart J Edelstein

Neuron 1998 10.1016/s0896-6273(00)80616-9

[17]

Tolu, S. et al. Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement. Mol. Psychiatry 18, 382–393 (2013). 10.1038/mp.2012.83

[18]

Picciotto, M. R. et al. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391, 173–177 (1998). 10.1038/34413

[19]

Maskos, U. et al. Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature 436, 103–107 (2005). 10.1038/nature03694

[20]

Frahm, S. et al. Aversion to nicotine is regulated by the balanced activity of β4 and α5 nicotinic receptor subunits in the medial habenula. Neuron 70, 522–535 (2011). 10.1016/j.neuron.2011.04.013

[21]

Harrington, L. et al. Role of β4* Nicotinic Acetylcholine Receptors in the Habenulo–Interpeduncular Pathway in Nicotine Reinforcement in Mice. 1–13, doi: 10.1038/npp.2015.346 (2015). 10.1038/npp.2015.346

[22]

Bierut, L. J. Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25. Trends in Pharmacological Sciences 31, 46–51 (2010). 10.1016/j.tips.2009.10.004

[23]

Sherva, R. et al. Variation in nicotinic acetylcholine receptor genes is associated with multiple substance dependence phenotypes. Neuropsychopharmacology 35, 1921–1931 (2010). 10.1038/npp.2010.64

[24]

Eddine, R. et al. A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine. Sci Rep 5, 8184 (2015). 10.1038/srep08184

[25]

Tizabi, Y., Copeland, R. L., Louis, V. A. & Taylor, R. E. Effects of combined systemic alcohol and central nicotine administration into ventral tegmental area on dopamine release in the nucleus accumbens. Alcoholism: Clinical and Experimental Research 26, 394–399 (2002). 10.1111/j.1530-0277.2002.tb02551.x

[26]

Tizabi, Y., Bai, L., Copeland, R. L. & Taylor, R. E. Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell. Alcohol and Alcoholism 42, 413–416 (2007). 10.1093/alcalc/agm057

[27]

Truitt, W. A. et al. Ethanol and nicotine interaction within the posterior ventral tegmental area in male and female alcohol-preferring rats: evidence of synergy and differential gene activation in the nucleus accumbens shell. Psychopharmacology 232, 639–649 (2015). 10.1007/s00213-014-3702-3

[28]

Doyon, W. M. et al. Nicotine Decreases Ethanol-Induced Dopamine Signaling and Increases Self-Administration via Stress Hormones. Neuron, doi: 10.1016/j.neuron.2013.06.006 (2013). 10.1016/j.neuron.2013.06.006

[29]

Leao, R. M. et al. Chronic Nicotine Activates Stress/Reward-Related Brain Regions and Facilitates the Transition to Compulsive Alcohol Drinking. J. Neurosci. 35, 6241–6253 (2015). 10.1523/jneurosci.3302-14.2015

[30]

Buisson, B. & Bertrand, D. Nicotine addiction: the possible role of functional upregulation. Trends in Pharmacological Sciences 23, 130–136 (2002). 10.1016/s0165-6147(00)01979-9

[31]

Funk, D., Marinelli, P. W. & Lê, A. D. Biological processes underlying co-use of alcohol and nicotine: neuronal mechanisms, cross-tolerance, and genetic factors. Alcohol Res Health 29, 186–192 (2006).

[32]

Clark, A. & Little, H. J. Interactions between low concentrations of ethanol and nicotine on firing rate of ventral tegmental dopamine neurones. Drug and Alcohol Dependence 75, 199–206 (2004). 10.1016/j.drugalcdep.2004.03.001

[33]

Engle, S. E., McIntosh, J. M. & Drenan, R. M. Nicotine and ethanol cooperate to enhance ventral tegmental area AMPA receptor function via α6-containing nicotinic receptors. Neuropharmacology 91, 13–22 (2015). 10.1016/j.neuropharm.2014.11.014

[34]

Rowell, P. P. & Li, M. Dose-response relationship for nicotine-induced up-regulation of rat brain nicotinic receptors. Journal of Neurochemistry 68, 1982–1989 (1997). 10.1046/j.1471-4159.1997.68051982.x

[35]

Marks, M. J. et al. Subsets of acetylcholine-stimulated 86Rb+ efflux and [125I]-epibatidine binding sites in C57BL/6 mouse brain are differentially affected by chronic nicotine treatment. Neuropharmacology 46, 1141–1157 (2004). 10.1016/j.neuropharm.2004.02.009

[36]

Besson, M. et al. Long-term effects of chronic nicotine exposure on brain nicotinic receptors. Proc. Natl. Acad. Sci. USA 104, 8155–8160 (2007). 10.1073/pnas.0702698104

[37]

Nashmi, R. et al. Chronic nicotine cell specifically upregulates functional alpha 4* nicotinic receptors: basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path. J. Neurosci. 27, 8202–8218 (2007). 10.1523/jneurosci.2199-07.2007

[38]

Metaxas, A. et al. Genetic deletion of the adenosine A(2A) receptor prevents nicotine-induced upregulation of α7, but not α4β2* nicotinic acetylcholine receptor binding in the brain. Neuropharmacology 71, 228–236 (2013). 10.1016/j.neuropharm.2013.03.023

[39]

Govind, A. P., Vezina, P. & Green, W. N. Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochemical Pharmacology 78, 756–765 (2009). 10.1016/j.bcp.2009.06.011

[40]

Tan, H., Bishop, S. F., Lauzon, N. M., Sun, N. & Laviolette, S. R. Chronic nicotine exposure switches the functional role of mesolimbic dopamine transmission in the processing of nicotine’s rewarding and aversive effects. Neuropharmacology 56, 741–751 (2009). 10.1016/j.neuropharm.2008.12.008

[41]

Caille, S., Guillem, K., Cador, M., Manzoni, O. & Georges, F. Voluntary Nicotine Consumption Triggers In Vivo Potentiation of Cortical Excitatory Drives to Midbrain Dopaminergic Neurons. J. Neurosci. 29, 10410–10415 (2009). 10.1523/jneurosci.2950-09.2009

[42]

Grieder, T. E. et al. Dopaminergic signaling mediates the motivational response underlying the opponent process to chronic but not acute nicotine. Neuropsychopharmacology 35, 943–954 (2010). 10.1038/npp.2009.198

[43]

Blomqvist, O., Ericson, M., Johnson, D. H., Engel, J. A. & Soderpalm, B. Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment. European Journal of Pharmacology 314, 257–267 (1996). 10.1016/s0014-2999(96)00583-3

[44]

Ding, Z.-M. et al. Repeated exposure of the posterior ventral tegmental area to nicotine increases the sensitivity of local dopamine neurons to the stimulating effects of ethanol. Alcohol 46, 217–223 (2012). 10.1016/j.alcohol.2011.11.007

[45]

Hauser, S. R. et al. Nicotine modulates alcohol-seeking and relapse by alcohol-preferring (P) rats in a time-dependent manner. Alcoholism: Clinical and Experimental Research 36, 43–54 (2012). 10.1111/j.1530-0277.2011.01579.x

[46]

Kamens, H. M., Andersen, J. & Picciotto, M. R. Modulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice. Psychopharmacology 208, 613–626 (2010). 10.1007/s00213-009-1759-1

[47]

Ericson, M., Molander, A., Löf, E., Engel, J. A. & Söderpalm, B. Ethanol elevates accumbal dopamine levels via indirect activation of ventral tegmental nicotinic acetylcholine receptors. European Journal of Pharmacology 467, 85–93 (2003). 10.1016/s0014-2999(03)01564-4

[48]

Larsson, A., Svensson, L., Söderpalm, B. & Engel, J. A. Role of different nicotinic acetylcholine receptors in mediating behavioral and neurochemical effects of ethanol in mice. Alcohol 28, 157–167 (2002). 10.1016/s0741-8329(02)00244-6

[49]

Patkar, O. L., Belmer, A., Tarren, J. R., Holgate, J. Y. & Bartlett, S. E. The effect of varenicline on binge-like ethanol consumption in mice is β4 nicotinic acetylcholine receptor-independent. Neuroscience Letters 633, 235–239 (2016). 10.1016/j.neulet.2016.09.048

[50]

Leeman, R. F. et al. Ethanol consumption: how should we measure it? Achieving consilience between human and animal phenotypes. Addict Biol 15, 109–124 (2010). 10.1111/j.1369-1600.2009.00192.x

Showing 50 of 55 references

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Published: Mar 23, 2017
Vol/Issue: 7(1)
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Authors

Renaud de Beaurepaire

P

Philippe Faure

Cite This Article

Stefania Tolu, Fabio Marti, Carole Morel, et al. (2017). Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors. Scientific Reports, 7(1). https://doi.org/10.1038/srep45116

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

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