Funk D, Marinelli PW, Le AD. Biological processes underlying co-use of alcohol and nicotine: neuronal mechanisms, cross-tolerance, and genetic factors. Alcohol Res Health 29: 186-192

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


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.

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Available from: Anh D Lê, Oct 12, 2015
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    • "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). "
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    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 · 5.36 Impact Factor
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    • "For example, pharmacological and/or genetic manipulation of various nAChRs such as α4β2*, α3β4*, and α3/α6β2* subtypes (* indicates the possible inclusion of other subunits) were shown to modulate ethanol selfadministration and ethanol-induced elevation of accumbal dopamine levels in rodents (Chatterjee et al., 2011; Hendrickson et al., 2010; Jerlhag et al., 2006; Kamens et al., 2010). Moreover, given the strong correlation between nicotine and ethanol abuse (DiFranza and Guerrera, 1990; Funk et al., 2006), it was further demonstrated that nicotine treatment re-instates ethanol seeking behaviors in rats following extinction of ethanol reinforcement (Lê et al., 2003; Hauser et al., 2012). In addition, nAChRs are previously shown to regulate deprivation-induced re-exposure of ethanol seeking in long-term ethanol experienced rats (Kuzmin et al., 2009; Rezvani et al., 2010). "
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    ABSTRACT: Relapse is a core feature of alcohol addiction and hinders the pharmacotherapy of alcohol use disorders. Pre-clinical and clinical studies have shown that neuronal nicotinic acetylcholine receptor (nAChR) partial agonists such as cytisine and its derivative, varenicline, reduce alcohol (ethanol) consumption and seeking behavior. However, the effects of these ligands on ethanol relapse are little understood. In the present study, we examined the effects of varenicline and cytisine on alcohol deprivation effect (ADE) - a validated model for relapse-like ethanol drinking in C57BL/6J mice. After habituation to 15% (v/v) ethanol intake using a continuous free-choice procedure, mice were exposed to alternating cycles of ethanol deprivation (5 days) and re-exposure (2 days). At the end of third deprivation cycle, animals received repeated intraperitoneal injections of saline, varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) and fluid intake was measured post 4 h and 24 h ethanol re-exposure. Repeated ethanol deprivation and re-exposure cycles significantly produced a robust and transient increase in ethanol (ADE). Pretreatment with varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) significantly reduced the expression of ADE at 4 h and 24 h after ethanol re-exposure. The results from this study indicate that nAChR partial agonists reduce the expression of ADE in mice and further suggest the involvement of nAChR mechanisms in ADE, a relapse-like ethanol drinking behavior.
    Pharmacology Biochemistry and Behavior 07/2013; 110. DOI:10.1016/j.pbb.2013.07.009 · 2.78 Impact Factor
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    • "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). "
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    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 · 15.05 Impact Factor
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