Varenicline Reduces Alcohol Self-Administration in Heavy-Drinking Smokers

McKee, Sherry A.; Harrison, Emily; O’Malley, Stephanie S.; Krishnan‐Sarin, Suchitra; Shi, Julia; Tetrault, Jeanette M.; Picciotto, Marina R.; Petrakis, Ismene L.; Estevez, Naralys; Balchunas, Erika

doi:10.1016/j.biopsych.2009.01.029

Cited by 280 publications

(310 citation statements)

References 44 publications

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“…These data are verified in clinical tests; thus blocking these subtypes, by using varenicline, reduces the intake of alcohol in heavy drinking smokers (McKee et al 2009) and one haplotype of the 6* gene is associated with heavy alcohol use ). Furthermore, it has been shown that excessive alcohol intake in rats consuming alcohol for a long period of time causes a release of acetylcholine in the VTA followed by an increase in accumbal dopamine levels, showing that alcohol like ghrelin activates the cholinergicdopaminergic reward link (Larsson et al 2005).…”

Section: The Central Ghrelin Signalling System Integrates With a Key mentioning

confidence: 71%

The role of the central ghrelin system in reward from food and chemical drugs

Dickson

Egecioglu

Landgren

et al. 2011

Molecular and Cellular Endocrinology

217

168

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Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Ghrelin administration into the VTA or LDTg activates the "cholinergicdopaminergic" reward link, suggesting that ghrelin may increase the incentive value of motivated behaviours such as reward-seeking behaviour ("wanting" or "incentive motivation"). Further, direct injection of ghrelin into the brain ventricles or into the VTA

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Section: The Central Ghrelin Signalling System Integrates With a Key mentioning

confidence: 71%

The role of the central ghrelin system in reward from food and chemical drugs

Dickson

Egecioglu

Landgren

et al. 2011

Molecular and Cellular Endocrinology

217

168

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“…We also showed that chlorzoxazone, an FDA-approved SK activator used for decades as a centrally acting myorelaxant, significantly reduces excessive alcohol intake in rats with intermittent access to ethanol, but does not reduce the more moderate alcohol intake in rats with continuous access to alcohol (Hopf et al, 2011). Alcohol intake in intermittent-access rats shows a number of other features, which have been considered to perhaps model some aspects of human alcoholism, including escalation of intake, sensitivity to compounds that reduce alcohol intake in human alcoholics (Steensland et al, 2007; Novel therapeutic strategies for addiction G Addolorato et al ............................................................................................................................................................... Simms et al, 2008;McKee et al, 2009) and aversion-resistant and perhaps compulsive alcohol intake (Hopf et al, 2010b). Thus, the SK activator chlorzoxazone may represent a potent and immediately accessible treatment for human alcoholism.…”

Section: Sk-type Calcium-activated Potassium Channelsmentioning

confidence: 99%

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

Addolorato

Leggio

Hopf

et al. 2011

Neuropsychopharmacol

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Drug addiction represents a major social problem where addicts and alcoholics continue to seek and take drugs despite adverse social, personal, emotional, and legal consequences. A number of pharmacological compounds have been tested in human addicts with the goal of reducing the level or frequency of intake, but these pharmacotherapies have often been of only moderate efficacy or act in a sub-population of humans. Thus, there is a tremendous need for new therapeutic interventions to treat addiction. Here, we review recent interesting studies focusing on gamma-aminobutyric acid receptors, voltage-gated ion channels, and transcranial magnetic stimulation. Some of these treatments show considerable promise to reduce addictive behaviors, or the early clinical studies or pre-clinical rationale suggest that a promising avenue could be developed. Thus, it is likely that within a decade or so, we could have important new and effective treatments to achieve the goal of reducing the burden of human addiction and alcoholism.

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“…VAR has been broadly implicated in the reduction of reward signaling, selectively decreasing voluntary alcohol intake in both rodents (Hendrickson et al, 2010;Steensland et al, 2007) and humans (Fucito et al, 2011;McKee et al, 2009). Administration of VAR decreases subjective reports of nicotine craving (Brandon et al, 2011;Patterson et al, 2009) and smoking cue-induced activity in the medial OFC (Franklin et al, 2011) in nontreatmentseeking smokers.…”

Section: Introductionmentioning

confidence: 99%

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers

Fedota

Salmeron

Ross

et al. 2015

Neuropsychopharmacol

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Recidivism rates for cigarette smokers following treatment often exceed 80%. Varenicline is the most efficacious pharmacotherapy currently available with cessation rates of 25-35% following a year of treatment. Although the in vivo binding properties are well known, varenicline's neurobiological mechanisms of action are still poorly understood. Varenicline acts as a nicotinic receptor partial agonist or antagonist depending on the presence or absence of nicotine and has been implicated in the reduction of reward signaling more broadly. The current study probed anticipatory reward processing using a revised monetary incentive delay task during fMRI in cohorts of smokers and non-smokers who completed a two-drug, placebo-controlled, double-blind crossover study. All participants underwent~17 days of order-balanced varenicline and placebo pill administration and were scanned under each condition wearing a transdermal nicotine or placebo patch. Consistent with nicotine's ability to enhance the rewarding properties of nondrug stimuli, acute nicotine administration enhanced activation in response to reward-predicting monetary cues in both smokers and non-smokers. In contrast, varenicline reduced gain magnitude processing, but did so only in smokers. These results suggest that varenicline's downregulation of anticipatory reward processing in smokers, in addition to its previously demonstrated reduction in the negative affect associated with withdrawal, independently and additively alter distinct brain circuits. These effects likely contribute to varenicline's efficacy as a pharmacotherapy for smoking cessation.

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Varenicline Reduces Alcohol Self-Administration in Heavy-Drinking Smokers

Cited by 280 publications

References 44 publications

The role of the central ghrelin system in reward from food and chemical drugs

The role of the central ghrelin system in reward from food and chemical drugs

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers

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