Potential substrates for nicotine and alcohol interactions: A focus on the mesocorticolimbic dopamine system

Abstract

Epidemiological studies consistently find correlations between nicotine and alcohol use, yet the neural mechanisms underlying their interaction remain largely unknown. Nicotine and alcohol (i.e., ethanol) share many common molecular and cellular targets that provide potential substrates for nicotine-alcohol interactions. These targets for interaction often converge upon the mesocorticolimbic dopamine system, where the link to drug self-administration and reinforcement is well documented. Both nicotine and alcohol activate the mesocorticolimbic dopamine system, producing downstream dopamine signals that promote the drug reinforcement process. While nicotine primarily acts via nicotinic acetylcholine receptors, alcohol acts upon a wider range of receptors and molecular substrates. The complex pharmacological profile of these two drugs generates overlapping responses that ultimately intersect within the mesocorticolimbic dopamine system to promote drug use. Here we will examine overlapping targets between nicotine and alcohol and provide evidence for their interaction. Based on the existing literature, we will also propose some potential targets that have yet to be directly tested. Mechanistic studies that examine nicotine-alcohol interactions would ultimately improve our understanding of the factors that contribute to the associations between nicotine and alcohol use.

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

“…This effect can be direct through nicotine action on nAChRs located within the dopaminergic system, 12 or indirect through, for example, recruitment of neuroendocrine systems. 42 Nicotine activates the hypothalamo-pituitary adrenal axis by primarily acting on neurons of the nucleus tractus solitarius projecting to the hypothalamus, which ultimately leads to the release of glucocorticoids hormones by the adrenal glands in both rodents and humans. 43,44 Glucocorticoids can then strengthen excitatory transmission onto VTA DA neurons.…”

Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine

“…The high occurrence of alcohol and tobacco co-abuse suggests that nicotine and alcohol share common mechanisms throughout the addiction process (Dani and Harris, 2005;Doyon et al, 2013b;Hurley et al, 2012;Rahman et al, 2014). Understanding the mechanisms of interaction between the two drugs has direct relevance for cessation strategies and treatment outcomes for alcoholics who are also addicted to nicotine.…”

“…In the NAc, acute administration of either ethanol or nicotine causes an increase in dopamine release, in part because of activation of nAChRs in the VTA (Doyon et al, 2013b). Concurrent, acute administration of nicotine and ethanol produces a synergistic effect leading to dopamine release that is significantly higher than that produced by each drug individually (Tizabi et al, 2007).…”

“…However, when nicotine administration precedes acute alcohol treatment, the ethanol-induced increases in dopamine release are attenuated and dopamine neuronal firing is suppressed in the VTA (Doyon et al, 2013a). Although the mechanisms underlying the acute interactions between alcohol and nicotine are being revealed (Doyon et al, 2013b), the effect of chronic nicotine treatment on ethanol-induced changes in dopamine levels and behavior needs further study.…”

Nicotine Infusion in the Wake‐Promoting Basal Forebrain Enhances Alcohol‐Induced Activation of Nucleus Accumbens

“…According to the World Health Organization, more than 7 million deaths every year are attributed to alcohol and nicotine use (WHO, 2013; WHO, 2008). Epidemiological studies suggest a shared vulnerability to nicotine and alcohol abuse whereby one substance influences the use of the other (Doyon et al, 2013). Approximately 90% of alcoholics smoke and approximately 60% of smokers consume substantial amount of alcohol (Batel et al, 1995; Dawson, 2000).…”