Effects of alcohol dependence on discrete choice between alcohol and saccharin

Russo, Melissa L.; Funk, Douglas; Loughlin, A.; Coen, Kathleen M.; Lê, A. D.

doi:10.1038/s41386-018-0101-1

Cited by 23 publications

(20 citation statements)

References 37 publications

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“…Only some 'vulnerable' animals show preferential drug choice [44][45][46]. Drug choice can be increased by extended drug exposure [47,48], and modified by manipulating the relative magnitude, delay or effort associated with the two rewards [49][50][51][52][53][54][55][56][57][58][59] and by the opportunity for social interaction [60,61]. Thus, drug choice is modified by individual differences, and multiple decision parameters relevant to that choice.…”

Section: Is Addiction Primarily Driven By Excessive Goal-directed Chomentioning

confidence: 99%

Addiction is driven by excessive goal-directed drug choice under negative affect: translational critique of habit and compulsion theory

Hogarth

2020

Neuropsychopharmacol.

219

158

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Drug addiction may be a goal-directed choice driven by excessive drug value in negative affective states, a habit driven by strong stimulus−response associations, or a compulsion driven by insensitivity to costs imposed on drug seeking. Laboratory animal and human evidence for these three theories is evaluated. Excessive goal theory is supported by dependence severity being associated with greater drug choice/economic demand. Drug choice is demonstrably goal-directed (driven by the expected value of the drug) and can be augmented by stress/negative mood induction and withdrawal-effects amplified in those with psychiatric symptoms and drug use coping motives. Furthermore, psychiatric symptoms confer risk of dependence, and coping motives mediate this risk. Habit theory of addiction has weaker support. Habitual behaviour seen in drug-exposed animals often does not occur in complex decision scenarios, or where responding is rewarded, so habit is unlikely to explain most human addictive behaviour where these conditions apply. Furthermore, most human studies have not found greater propensity to habitual behaviour in drug users or as a function of dependence severity, and the minority that have can be explained by task disengagement producing impaired explicit contingency knowledge. Compulsion theory of addiction also has weak support. The persistence of punished drug seeking in animals is better explained by greater drug value (evinced by the association with economic demand) than by insensitivity to costs. Furthermore, human studies have provided weak evidence that propensity to discount cost imposed on drug seeking is associated with dependence severity. These data suggest that human addiction is primarily driven by excessive goal-directed drug choice under negative affect, and less by habit or compulsion. Addiction is pathological because negative states powerfully increase expected drug value acutely outweighing abstinence goals.

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Section: Is Addiction Primarily Driven By Excessive Goal-directed Chomentioning

confidence: 99%

Addiction is driven by excessive goal-directed drug choice under negative affect: translational critique of habit and compulsion theory

Hogarth

2020

Neuropsychopharmacol.

219

158

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“…in the alcohol vapor group were placed sealed chambers (La Jolla Alcohol Research) and exposed to alcohol vapor introduced into the chambers by air pumped continuously over heated 95% alcohol (Russo et al, 2018). These rats received daily exposures (14 h alcohol vapor; 10 h air) in the chambers for 4 d/week (Tuesday-Friday) and were placed in their home cages on the weekend, for 6 weeks.…”

Section: Alcohol Vapor Chambers-ratsmentioning

confidence: 99%

Effect of chronic alcohol vapor exposure on reinstatement of alcohol seeking induced by U50,488

et al. 2019

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Alcohol dependence and stress are associated with relapse to alcohol during abstinence, but the underlying mechanisms are poorly understood. Kappa opioid receptors (KOR) are involved in alcohol reward and in the effects of stress. Previously, in non-dependent rats, we showed that KOR in the bed nucleus of the stria terminalis (BNST) mediate reinstatement of alcohol seeking induced by the selective KOR agonist U50,488. Here, we determine the effects of chronic, intermittent exposure to alcohol vapor on U50,488-induced reinstatement of alcohol seeking. We also study brain mechanisms involved using the neuronal activity marker Fos and phosphorylated p38 MAPK (p-p38), an intracellular messenger implicated in the effects of KOR stimulation. We trained male Long-Evans rats to self-administer alcohol (12% w/v) and exposed them to alcohol vapor (14 h vapor/10 h air) daily for 24 d or to the control condition, extinguished alcohol-reinforced responding and determined the dose response for U50,488-induced reinstatement. We then determined the effects of vapor exposure on U50,488-induced Fos and p-p38 expression. Vaporexposed rats were more sensitive to U50,488-induced reinstatement. U50,488 increased Fos expression in brain areas involved in stress-induced relapse, and Fos activation in the ventral BNST was greater in vapor exposed rats. Vapor exposed rats had increased basal p-p38 expression in the dorsal BNST, LC and NTS. Our findings suggest that changes in the neuronal responses to KOR stimulation in the ventral BNST may be involved in the increased sensitivity to U50,488 accompanying dependence.

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“…In this condition, the large majority of rats prefer the alternative nondrug reward. This finding, first discovered more than 10 years ago (Lenoir et al, 2007), was repeatedly reproduced in a large set of conditions, including: different drug and nondrug rewards; various drug doses and history of drug self-administration; different reward delays and costs (Augier et al, 2012;Cantin et al, 2010;Caprioli et al, 2015;Huynh et al, 2017;Kearns et al, 2017;Kerstetter et al, 2012;Lenoir et al, 2013b;Lenoir and Ahmed, 2008;Madsen and Ahmed, 2015;Pelloux and Baunez, 2017;Russo et al, 2018;Schwartz et al, 2017;Venniro et al, 2018). However, in a free-operant choice schedule in which both options are continuously available, and thus, in which choosing under the drug influence is permitted, choice behavior dramatically differs (Bozarth and Wise, 1985;Freese et al, 2018;Thomsen et al, 2013Thomsen et al, , 2008Vandaele et al, 2016).…”

Section: Introductionmentioning

confidence: 83%

Choosing between cocaine and sucrose under the influence: testing the effect of cocaine tolerance

Vandaele¹,

Ahmed

2021

Preprint

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Cocaine use not only depends on the reinforcing properties of the drug, but also on its intoxicating effects on alternative nondrug activities. In animal models investigating choice between cocaine and alternative sweet rewards, the latter influence can have a dramatic impact on choice outcomes. When cocaine intoxication at the moment of choice is prevented by imposing sufficiently long intervals between choice trials, animals typically prefer the sweet reward. However, when choosing under the drug influence is permitted, animals shift their preference in favor of cocaine. We previously hypothesized that this preference shift is mainly due to a direct suppression of responding for sweet reward by cocaine intoxication. Here we tested this hypothesis by making rats tolerant to this drug-induced behavioral suppression. Contrary to our expectation, tolerance did not prevent rats from shifting their preference to cocaine when choosing under the influence. Thus, other mechanisms must be invoked to explain the influence of cocaine intoxication on choice outcomes.

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Effects of alcohol dependence on discrete choice between alcohol and saccharin

Cited by 23 publications

References 37 publications

Addiction is driven by excessive goal-directed drug choice under negative affect: translational critique of habit and compulsion theory

Addiction is driven by excessive goal-directed drug choice under negative affect: translational critique of habit and compulsion theory

Effect of chronic alcohol vapor exposure on reinstatement of alcohol seeking induced by U50,488

Choosing between cocaine and sucrose under the influence: testing the effect of cocaine tolerance

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