Biological processes underlying co-use of alcohol and nicotine: Neuronal mechanisms, cross-tolerance, and genetic factors

Centre for Addiction and Mental Health, Toronto, Canada.
Alcohol research & health: the journal of the National Institute on Alcohol Abuse and Alcoholism (Impact Factor: 0.58). 02/2006; 29(3):186-92.
Source: PubMed

ABSTRACT Alcohol and nicotine are two of the oldest and most commonly used recreational drugs, and many people use both of them together. Although their ready availability likely contributes to the strong correlation between alcohol and nicotine use, several lines of evidence suggest that biological factors play a role as well. For example, both alcohol and nicotine act on a brain system called the mesolimbic dopamine system, which mediates the rewarding and reinforcing properties of both drugs. Modification of the activities of the mesolimbic dopamine system can interfere with the effects of both alcohol and nicotine. Another mechanism that may contribute to alcohol-nicotine interactions is cross-tolerance to the effects of both drugs. Finally, genetic studies in humans and of selectively bred mouse and rat strains suggest that shared genetic factors help determine a person's liability to use or abuse both alcohol and nicotine.

Download full-text


Available from: Anh D Lê, Aug 30, 2015
  • Source
    • "It is thus possible that the minor allele of the rs2948694 alters the sensitivity of the cholinergic-dopaminergic reward link, which in turn may lead to a predisposition to smoking and increased alcohol consumption, reflected by the higher AUDIT scores in the present study. Previous studies show that alcohol and nicotine dependence share a genetic background (True et al. 1999; Funk, Marinelli & Le 2006; von der Pahlen et al. 2008). This is further supported by the welldocumented co-use of alcohol and nicotine—also observed in the present study—and the neurobiological interaction between alcohol and nicotine within the mesolimbic dopamine system (for review, see Larsson & Engel 2004; Soderpalm, Lof & Ericson 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The multifaceted gut-brain peptide ghrelin and its receptor (GHSR-1a) are implicated in mechanisms regulating not only the energy balance but also the reward circuitry. In our pre-clinical models, we have shown that ghrelin increases whereas GHSR-1a antagonists decrease alcohol consumption and the motivation to consume alcohol in rodents. Moreover, ghrelin signaling is required for the rewarding properties of addictive drugs including alcohol and nicotine in rodents. Given the hereditary component underlying addictive behaviors and disorders, we sought to investigate whether single nucleotide polymorphisms (SNPs) located in the pre-proghrelin gene (GHRL) and GHSR-1a gene (GHSR) are associated with alcohol use, measured by the alcohol use disorders identification test (AUDIT) and smoking. Two SNPs located in GHRL, rs4684677 (Gln90Leu) and rs696217 (Leu72Met), and one in GHSR, rs2948694, were genotyped in a subset (n = 4161) of a Finnish population-based cohort, the Genetics of Sexuality and Aggression project. The effect of these SNPs on AUDIT scores and smoking was investigated using linear and logistic regressions, respectively. We found that the minor allele of the rs2948694 SNP was nominally associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model). Furthermore, post hoc analyses showed that this risk allele was also associated with increased likelihood of having high level of alcohol problems as determined by AUDIT scores ≥ 16 (P = 0.0043, recessive model). These convergent findings lend further support for the hypothesized involvement of ghrelin signaling in addictive disorders. © 2015 Society for the Study of Addiction.
    Addiction Biology 07/2015; DOI:10.1111/adb.12277 · 5.93 Impact Factor
  • Source
    • "In addition to psychosocial and genetic factors (Bobo and Husten, 2000; Schlaepfer et al., 2008), evidence suggests that the interactions between nicotine and alcohol arise from shared pharmacological actions (Funk et al., 2006; Hurley et al., 2012; Larsson and Engel, 2004). These drugs activate common neural substrates, including the mesolimbic dopamine (DA) system (De Biasi and Dani, 2011; Di Chiara, 2000; Gonzales et al., 2004) and the hypothalamic-pituitary-adrenal (HPA) axis associated with stress hormone signaling (Armario, 2010; Lutfy et al., 2012; Richardson et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tobacco smoking is a well-known risk factor for subsequent alcohol abuse, but the neural events underlying this risk remain largely unknown. Alcohol and nicotine reinforcement involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to nicotine increases alcohol self-administration and decreases alcohol-induced dopamine responses. The blunted dopamine response was due to increased inhibitory synaptic transmission onto dopamine neurons. Blocking stress hormone receptors prior to nicotine exposure prevented all interactions with alcohol that we measured, including the increased inhibition onto dopamine neurons, the decreased dopamine responses, and the increased alcohol self-administration. These results indicate that nicotine recruits neuroendocrine systems to influence neurotransmission and behavior associated with alcohol reinforcement.
    Neuron 07/2013; 79(3). DOI:10.1016/j.neuron.2013.06.006 · 15.98 Impact Factor
  • Source
    • "Tobacco, specifically nicotine, and alcohol are often co-abused substances. Several lines of evidence suggest shared biological and genetic mechanisms [1], [2]. Data obtained from genetic studies utilizing twins and families support the idea that there is a strong contribution from common genetic factors [3], [4], [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Common genetic factors strongly contribute to both nicotine, the main addictive component of tobacco, and alcohol use. Several lines of evidence suggest nicotinic acetylcholine receptors as common sites of action for nicotine and alcohol. Specifically, rs1948, a single-nucleotide polymorphism (SNP) located in the CHRNB4 3'-untranslated region (UTR), has been associated to early age of initiation for both alcohol and tobacco use. To determine the allelic effects of rs1948 on gene expression, two rs1948-containing sequences of different lengths corresponding to the CHRNB4 3'-UTR were cloned into pGL3-promoter luciferase reporter vectors. Data obtained showed that the allelic effects of SNP rs1948 on luciferase expression are mediated by the length and species of transcripts generated. In addition, it was found that miR-3157 increased the overall luciferase expression while miR-138, a microRNA known to play a role in neuroadaptation to drug abuse, decreased luciferase expression when compared to basal conditions. These findings demonstrate the importance of SNP rs1948 on the regulation of CHRNB4 expression and provide the first evidence of CHRNB4 down-regulation by miR-138.
    PLoS ONE 05/2013; 8(5):e63699. DOI:10.1371/journal.pone.0063699 · 3.23 Impact Factor
Show more