Reward, Addiction, Withdrawal to Nicotine

Biasi, Mariella De; Dani, John A.

doi:10.1146/annurev-neuro-061010-113734

Cited by 310 publications

(314 citation statements)

References 284 publications

(411 reference statements)

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“…Chronic nicotine is known to up-regulate a4b2* nAChRs in the striatum, thereby increasing dopamine release from dopaminergic terminals (Changeux, 2010). Nicotine's action on these receptors, and a6 receptors, causes a shift in the firing patterns of dopaminergic neurons from tonic, low frequency single-spike firing, to phasic, longer high frequency firing (De Biasi and Dani, 2011). A disproportionate decrease in the tonic firing compared with the phasic signals is also observed in the nucleus accumbens during withdrawal from chronic nicotine (Zhang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Hilário

Turner

Blendy

2012

Neuropsychopharmacol

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Tobacco dependence is an addiction with high rates of relapse, resulting in multiple quit attempts in individuals who are trying to stop smoking. How these multiple cycles of smoking and withdrawal contribute to nicotine dependence, long-term alterations in brain reward systems, and nicotine receptor regulation is unknown. Therefore, to evaluate how multiple exposures of nicotine and withdrawal periods modulate rewarding properties of nicotine, we used intracranial self-stimulation to measure alterations in the threshold of brain stimulation reward. In addition, we employed the conditioned place preference (CPP) paradigm to evaluate positive context conditioning following each withdrawal period and measured levels of neuronal nicotinic receptors in cortex, striatum, and hippocampus. We found that repeated nicotine exposure and withdrawal enhanced brain stimulation reward and reward sensitivity to acute injections of nicotine. This increased reward was reflected by enhanced CPP to nicotine. Chronic nicotine is known to up-regulate nAChRs (nicotinic acetylcholine receptors) and we found that this up-regulation was maintained for up to 8 days of withdrawal in the striatum and in the hippocampus, but not in the cortex, of animals exposed to multiple nicotine exposure and withdrawal periods. These results demonstrate that repeated exposures to nicotine, followed by withdrawal, induce a persistent increase in both brain reward function and sensitivity to the hedonic value of nicotine and long-lasting up-regulation of neuronal nicotinic receptors. Together, these data suggest that a continuing increase in brain reward function and enhanced sensitivity to nicotine reward following repeated withdrawal periods may be one reason why smokers relapse frequently.

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Section: Discussionmentioning

confidence: 99%

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Hilário

Turner

Blendy

2012

Neuropsychopharmacol

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“…The MCL consists predominantly of dopaminergic projections from the midbrain ventral tegmental area to limbic and cortical projection fields in nucleus accumbens (NAc), amygdala, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). In the case of tobacco smoking, reinforcing and subsequent addictive effects of nicotine are the result of neuronal acetylcholine receptor (nAChR) activation that modulates 'downstream' events including increased MCL dopamine (DA) release (Tapper et al, 2004;De Biasi and Dani, 2011). The addictive propensity of nicotine is theorized to be due to its quick but short-lived agonistic effect on nAChRs containing α4 and β2 subunits located on the presynaptic membrane of DA neurons (Exley et al, 2011;Tapper et al, 2004).…”

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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“…These mappings are critical in conditions like drug addiction, where our ignorance of how prior beliefs about drugs influence physiological processes related to drugs of abuse presents a profound challenge to the understanding of the mechanism and treatment of addiction (2,3). Although extensive work has shown that addictive drugs act on the mesolimbic dopaminergic (DA) pathway (2,4), it has become clear that these purely biochemical explanations are not sufficient to account for the huge heterogeneity among drug-dependent individuals and the low success rate of quitting and remaining drug-free (2,5) and that cognitive factors such as beliefs and expectations have a profound impact on drug-related neurobiological effects (6,7).…”

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confidence: 99%

“…Striatal DA levels are also modulated by prediction errors about alcohol (21). It is thus reasonable to suspect that beliefs about nicotine could modulate the key neural signals involved in nicotine addiction (4,31). These same neural signals that guide Significance Nicotine is the primary addictive substance in tobacco, which stimulates neural pathways mediating reward processing.…”

mentioning

confidence: 99%

“…Our findings suggest that subjective beliefs can override the physical presence of a powerful drug like nicotine by modulating learning signals processed in the brain's reward system. learning also guide choice behavior (32,33) and are disrupted in nicotine addiction (4,31,(34)(35)(36)(37). Thus, factors that might modulate neural signals in the striatum, such as smokers' prior beliefs, could also impact reinforcement learning behavior in smokers.…”

mentioning

confidence: 99%

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Belief about nicotine selectively modulates value and reward prediction error signals in smokers

Lohrenz

Salas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Little is known about how prior beliefs impact biophysically described processes in the presence of neuroactive drugs, which presents a profound challenge to the understanding of the mechanisms and treatments of addiction. We engineered smokers' prior beliefs about the presence of nicotine in a cigarette smoked before a functional magnetic resonance imaging session where subjects carried out a sequential choice task. Using a model-based approach, we show that smokers' beliefs about nicotine specifically modulated learning signals (value and reward prediction error) defined by a computational model of mesolimbic dopamine systems. Belief of "no nicotine in cigarette" (compared with "nicotine in cigarette") strongly diminished neural responses in the striatum to value and reward prediction errors and reduced the impact of both on smokers' choices. These effects of belief could not be explained by global changes in visual attention and were specific to value and reward prediction errors. Thus, by modulating the expression of computationally explicit signals important for valuation and choice, beliefs can override the physical presence of a potent neuroactive compound like nicotine. These selective effects of belief demonstrate that belief can modulate modelbased parameters important for learning. The implications of these findings may be far ranging because belief-dependent effects on learning signals could impact a host of other behaviors in addiction as well as in other mental health problems.O ne materialist view of mental function suggests that even the most abstract beliefs can be represented in terms of physiological states available to the brain (1). These mappings are critical in conditions like drug addiction, where our ignorance of how prior beliefs about drugs influence physiological processes related to drugs of abuse presents a profound challenge to the understanding of the mechanism and treatment of addiction (2, 3). Although extensive work has shown that addictive drugs act on the mesolimbic dopaminergic (DA) pathway (2, 4), it has become clear that these purely biochemical explanations are not sufficient to account for the huge heterogeneity among drug-dependent individuals and the low success rate of quitting and remaining drug-free (2, 5) and that cognitive factors such as beliefs and expectations have a profound impact on drug-related neurobiological effects (6, 7).Beliefs are known to contribute to the placebo effect. The placebo effect is a treatment effect not caused by the physical presence of an active drug, but rather by the meaning ascribed to it and the subjective expectation of receiving a treatment (8, 9). A subject's belief that he or she is receiving a treatment could lead to observable improvement even in the absence of active drugs. These treatment effects are putatively accomplished by neurobiological processes usually associated with pharmacological actions of active drugs, even though active drugs are not administered (10-14). Interestingly, beliefs also directly impact behavioral...

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Reward, Addiction, Withdrawal to Nicotine

Cited by 310 publications

References 284 publications

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers

Belief about nicotine selectively modulates value and reward prediction error signals in smokers

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