Human studies of the behavioral pharmacological determinants of nicotine dependence.

Je, Henningfield; Goldberg,; Ri, H. dal; Dr, Jasinski; Lukas, SE; Miyasato, K; Nemeth-Coslett, R.; Wb, Pickworth; Je, Rose; Sampson, Anthony P.

doi:10.1037/e469432004-001

Cited by 6 publications

(5 citation statements)

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“…Indeed, the plasma concentrations achieved by self-administering wildtype mice are comparable to those achieved in humans after 5 hours of smoking their preferred cigarette (Fowler and Kenny, 2011; Fowler et al, 2011; Matta et al, 2007; Russell et al, 1975). Moreover, self-administration of intravenous nicotine in both rodents and humans decreases when higher doses of the drug are provided (Fowler and Kenny, 2011; Harvey et al, 2004), similar to that found with cigarette smoking in humans (Henningfield and Goldberg, 1983a; Henningfield et al, 1986; Russell et al, 1975). These data, combined with the findings that altered expression of the α5* nAChRs in mice, rats and humans results in a similar behavior profile in relation to nicotine consumption, support the contention that aversion induced by nicotine is likely conserved across species.…”

Section: The Chrna5-chrna3-chrnb3 Gene Cluster and Nicotine Aversionsupporting

confidence: 60%

“…Indeed, when levels of nicotine contained in tobacco are varied, smokers are far more efficient at titrating their intake downwards when consuming high-nicotine-content tobacco to avoid noxious effects of the drug (Henningfield and Goldberg, 1983a; Henningfield et al, 1986; Russell et al, 1975), than they are at adjusting their intake upward to compensate for reduced nicotine in low-content tobacco (Sutton et al, 1978). Hence, self-regulation of consumption to avoid noxious effects of nicotine is far better regulated that compensation upwards to avoid a reduction in nicotine intake.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

2014

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Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action is considered critical in establishing and maintaining the tobacco smoking habit. Compounds that attenuate nicotine reward are considered promising therapeutic candidates for tobacco dependence, but many of these agents have other actions that limit their potential utility. Nicotine is also highly noxious, particularly at higher doses, and aversive reactions to nicotine after initial exposure can decrease the likelihood of developing a tobacco habit in many first time smokers. Nevertheless, relatively little is known about the mechanisms of nicotine aversion. The purpose of this review is to present recent new insights into the neurobiological mechanisms that regulate avoidance of nicotine. First, the role of the mesocorticolimbic system, so often associated with nicotine reward, in regulating nicotine aversion is highlighted. Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed. Third, the role of the habenular complex in nicotine aversion, primarily medial habenular projections to the interpeduncular nucleus (IPN) but also lateral habenular projections to rostromedial tegmental nucleus (RMTg) and ventral tegmental area (VTA) are reviewed. Forth, brain circuits that are enriched in nAChRs, but whose role in nicotine avoidance has not yet been assessed, will be proposed. Finally, the feasibility of developing novel therapeutic agents for tobacco dependence that act not by blocking nicotine reward but by enhancing nicotine avoidance will be considered.

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Section: The Chrna5-chrna3-chrnb3 Gene Cluster and Nicotine Aversionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

2014

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“…Nicotine, including that contained in tobacco smoke, has aversive effects, with non-human primates and human tobacco smokers demonstrating avoidance of the drug particularly when higher unit doses are available for consumption. It is important to note that even doses of nicotine that are actively self-administered by non-human primates or humans can be aversive and trigger avoidance behaviors (Goldberg and Spealman 1982; 1983; Goldberg et al 1981; Goldberg et al 1983; Henningfield and Goldberg 1983; Henningfield et al 1986; Spealman and Goldberg 1982). This suggests that the reward-enhancing and reward-inhibiting effects of nicotine occur concurrently, with the reward-inhibiting effects that suppress nicotine intake becoming more marked as the unit dose of nicotine available for consumption increases (Fowler et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Role of α5* nicotinic acetylcholine receptors in the effects of acute and chronic nicotine treatment on brain reward function in mice

2013

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Objective Allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) subunit gene, CHRNA5, increases vulnerability to tobacco addiction. Here, we investigated the role of α5* nAChRs in the effects of nicotine on brain reward systems. Materials and methods Effects of acute (0.03125-0.5 mg/kg SC) or chronic (24 mg/kg per day; osmotic minipump) nicotine, and mecamylamine-precipitated withdrawal, on intracranial self-stimulation (ICSS) thresholds were assessed in wildtype and α5 nAChR subunit knockout mice. Noxious effects of nicotine were further investigated using a conditioned taste aversion (CTA) procedure. Results Lower nicotine doses (0.03125-0.125 mg/kg) decreased ICSS thresholds in wildtype and α5 knockout mice. At higher doses (0.25-0.5 mg/kg), threshold-lowering effects of nicotine were diminished in wildtype mice, whereas nicotine lowered thresholds across all doses tested in α5 knockout mice. Nicotine (1.5 mg/kg) conditioned a taste aversion to saccharine equally in both genotypes. Mecamylamine (5 mg/kg) elevated ICSS thresholds by a similar magnitude in wildtype and α5 knockout mice prepared with minipumps delivering nicotine. Unexpectedly, mecamylamine also elevated thresholds in saline-treated α5 knockout mice. Conclusion α5* nAChRs are not involved in reward-enhancing effects of lower nicotine doses, the reward-inhibiting effects of nicotine withdrawal, or the general noxious effects of higher nicotine doses. Instead, α5* nAChRs regulate the reward-inhibiting effects nicotine doses that oppose the reward-facilitating effects of the drug. These data suggest that disruption of α5* nAChR signaling greatly expands the range of nicotine doses that facilitate brain reward activity, which may help explain the increased tobacco addiction vulnerability associated with CHRNA5 risk alleles.

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“…Studies evaluating cigarettes that vary across a range of doses suggest that pleasurable subjective effects typically increase as a function of dose (Benowitz, Jacob, & Herrera, 2006; Hatsukami et al, 2013a; Higgins et al, 2017). Subjective experiences of nicotine toxicity may also be dose-dependent, with higher nicotine content cigarettes producing greater aversive effects (Benowitz et al, 2006; Henningfield et al, 1986; Pickworth, Moolchan, Berlin, & Murty, 2002). Conversely, dose effects appear to be less pronounced on scales assessing craving and withdrawal (Hatsukami et al, 2013a; Pickworth et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Preliminary validity of the modified Cigarette Evaluation Questionnaire in predicting the reinforcing effects of cigarettes that vary in nicotine content.

Arger

Heil

Sigmon

et al. 2017

Experimental and Clinical Psychopharmacology

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Validity studies evaluating self-report measures in relation to behavioral preference of cigarettes varying in nicotine content are needed. The current study examined the relationship between ratings on the modified Cigarette Evaluation Questionnaire (mCEQ) and the relative reinforcing effects of Spectrum research cigarettes (15.8, 5.2, 2.4, 0.4 milligrams per gram of tobacco). Data for this secondary analysis were obtained from a double-blind study (Higgins et al., 2017) evaluating the subjective and reinforcing effects of Spectrum cigarettes under acute smoking abstinence. Current smokers (N=26) were recruited from three vulnerable smoking populations (economically-disadvantaged women of reproductive age, opioid-maintained individuals, individuals with affective disorders). In Phase 1 (5 sessions), the mCEQ (Satisfaction, Psychological Reward, Enjoyment of Respiratory Tract Sensations, Craving Reduction, Aversion subscales) was administered following ad-lib smoking of Spectrum cigarettes and subscale differences scores were calculated by subtracting ratings of the 15.8 mg/g cigarette from ratings of the reduced nicotine content cigarettes. In Phase 2 (6 sessions), participants completed six two-dose concurrent choice tests. The relationship between mCEQ subscale difference scores from Phase 1 and nicotine dose choice from Phase 2 was examined using mixed-model repeated-measures analyses of variance. Higher Satisfaction and lower Aversion subscale difference scores were associated with choosing the 15.8 mg/g cigarette more than the 5.2, 2.4, and 0.4 mg/g cigarettes. Scores on the other mCEQ subscales were not associated with nicotine choice. These results provide support for validity of the mCEQ Satisfaction and Aversion subscales predicting the relative reinforcing effects and abuse liability of varying nicotine content cigarettes.

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Human studies of the behavioral pharmacological determinants of nicotine dependence.

Cited by 6 publications

References 0 publications

Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

Role of α5* nicotinic acetylcholine receptors in the effects of acute and chronic nicotine treatment on brain reward function in mice

Preliminary validity of the modified Cigarette Evaluation Questionnaire in predicting the reinforcing effects of cigarettes that vary in nicotine content.

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