The biological, social and clinical bases of drug addiction: commentary and debate

Altman, Jennifer; Everitt, Barry J.; Glautier, Steven; Markou, Athina; Nutt, David; Oretti, Rossana; Phillips, G. D.; Robbins, Trevor W.

doi:10.1007/bf02246016

Cited by 254 publications

(175 citation statements)

References 271 publications

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“…If we accept the concept that some of the individuals who abuse alcohol do so in part because of the changes the drug induces in their C NS, it seems reasonable to propose that if such changes cannot be achieved with a given dose of alcohol, these individuals may consume more of the drug in an attempt to regain the wanted changes. A drug exerts its reinforcing effects via a number of distinct actions, including the ability to stimulate brain circuitries involved in the reward system and to induce symptoms of withdrawal that can only be averted by resuming drug consumption (Nestler et al, 1993;Altman et al, 1996;Koob, 1996). We suggest that our studies may provide the basis for a testable, neuroendocrine-based hypothesis of vulnerability to alcohol abuse.…”

Section: Discussionmentioning

confidence: 82%

An Initial, Three-Day-Long Treatment with Alcohol Induces a Long-Lasting Phenomenon of Selective Tolerance in the Activity of the Rat Hypothalamic–Pituitary–Adrenal Axis

Lee

Rivier

1997

J. Neurosci.

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We determined whether an initial alcohol challenge induced long-lasting changes in the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Adult male rats received intragastric injections of the vehicle or a moderately intoxicating dose of alcohol (3.0 gm/kg) daily for 3 d. When animals were acutely challenged with alcohol 3-12 d later, their ACTH and corticosterone responses were significantly blunted, compared with that of vehicle-pretreated rats. In contrast, exposure to mild electric foot shocks induced a pattern of ACTH secretion that was comparable in animals administered alcohol or the vehicle previously, indicating a lack of cross-tolerance. No significant differences were observed in pituitary responsiveness to corticotropin-releasing factor or vasopressin in rats pretreated with the vehicle or alcohol. The influence of the initial drug treatment was not mimicked by exposure to foot shocks, nor was it prevented by administering a potent corticotropinreleasing factor antagonist to block the elevations in plasma ACTH and corticosterone induced by this initial treatment. Finally, we found that rats injected initially with the vehicle and challenged subsequently with alcohol exhibited the expected increased neuronal activation (measured by the upregulation of steady-state mRNA and protein levels of immediate early genes) in the paraventricular nucleus of their hypothalamus. In contrast, this response was markedly decreased in animals exposed previously to the drug.To our knowledge, this is the first report that exposure to a stress (i.e., alcohol), although not immediately altering the response of the HPA axis to this particular signal, induces a selective tolerance that is both slow to develop and longlasting. The primary mechanism mediating the ability of an initial drug treatment to decrease subsequent responses of the HPA axis to a second drug challenge seems to be the inability of hypothalamic neurons to respond adequately to this second challenge.

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Section: Discussionmentioning

confidence: 82%

An Initial, Three-Day-Long Treatment with Alcohol Induces a Long-Lasting Phenomenon of Selective Tolerance in the Activity of the Rat Hypothalamic–Pituitary–Adrenal Axis

Lee

Rivier

1997

J. Neurosci.

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“…Koob and Nestler, 1997) but are hypoactive in abstinent drug users (e.g. Altmann et al, 1996;Volkow et al, 2004). Disturbances of the cognitive and behavioural processes mediated by these pathways, including attribution of salience to external stimuli and inhibitory control over behaviour, may contribute both to the development of dependence and to relapse.…”

Section: Introductionmentioning

confidence: 99%

Relapse to smoking during unaided cessation: clinical, cognitive and motivational predictors

et al. 2010

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Rationale: Neurobiological models of addiction suggest that abnormalities of brain reward circuitry distort salience attribution and inhibitory control processes, which in turn contribute to high relapse rates. Objectives:To determine whether impairments of salience attribution and inhibitory control predict relapse in a pharmacologically unaided attempt at smoking cessation.Methods: 141 smokers were assessed on indices of nicotine consumption / dependence (e.g. the FTND, cigarettes per day, salivary cotinine), and three trait impulsivity measures. After overnight abstinence they completed experimental tests of cue reactivity, attentional bias to smoking cues, response to financial reward, motor impulsiveness, and response inhibition (antisaccades). They then started a quit attempt with follow-up after 7 days, 1 month, and 3 months; abstinence was verified via salivary cotinine levels ≤ 20ng/ml. Results:Relapse rates at each point were 52.5%, 64% and 76.3%. The strongest predictor was pre-cessation salivary cotinine; other smoking / dependence indices did not explain additional outcome variance and neither did trait impulsivity. All experimental indices except responsivity to financial reward significantly predicted one week outcome. Salivary cotinine, attentional bias to smoking cues and antisaccade errors explained unique as well as shared variance. At one and three months, salivary cotinine, motor impulsiveness and cue reactivity were all individually predictive; the effects of salivary cotinine and motor impulsiveness were additive.Conclusions: These data provide some support for the involvement of abnormal cognitive and motivational processes in sustaining smoking dependence and suggest that they might be a focus of interventions, especially in the early stages of cessation.2

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“…In smokers, for instance, Geracioti et al (1999) found abnormally low levels of a DA metabolite in cerebrospinal fluid. Reviewing an international symposium on this topic, Altmann et al (1996) concluded that "withdrawal from various drugs of abuse is associated with a reduction in dopamine transmission in the ventral striatum, an effect that is opposite to the common property of drugs of abuse to stimulate dopamine transmission. "…”

Section: Effects Of Smoking and Abstinence On Functioning Of Brain Rementioning

confidence: 99%

Smoking, reward responsiveness, and response inhibition: tests of an incentive motivational model

Powell

Dawkins

Davis

2002

Biological Psychiatry

126

114

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Background: Incentive-motivation models of addiction suggest impairment of functional activity in mesocorticolimbic reward pathways during abstinence. This study tested implications for subjective and behavioral responses to nondrug incentives, cue-elicited craving, and prefrontal cognitive functions, particularly response inhibition. Methods:We tested 26 smokers after smoking and after overnight abstinence in counterbalanced order; 26 nonsmokers were also tested twice. Measures included a simple card-sorting test performed with and without financial incentive (the CARROT), the Snaith Hamilton Pleasure Scale as an index of subjective reward responsiveness, ratings of subjective craving and withdrawal before and after exposure to a cigarette, an index of oculomotor response inhibition (saccadic vs. antisaccadic eye movements), verbal fluency, and reversed digit span. Results:Compared with the smoking condition, and independently of withdrawal severity, abstinence was associated with reduced cue reactivity, pleasure expectancies, responsiveness to financial incentive, and response inhibition (antisaccadic eye movements). Verbal fluency and reversed digit span were unaffected, contrary to findings elsewhere with heavier smokers. Nonsmokers' scores either fell between those of abstainers and recent smokers or approximated those of recent smokers. Conclusions:The data were in general consistent with behavioral predictions derived from the incentive-motivational model of addiction and suggest that abstinence may be associated with impairments of motivation and response inhibition, which are independent of other subjectively experienced withdrawal symptoms.

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The biological, social and clinical bases of drug addiction: commentary and debate

Cited by 254 publications

References 271 publications

An Initial, Three-Day-Long Treatment with Alcohol Induces a Long-Lasting Phenomenon of Selective Tolerance in the Activity of the Rat Hypothalamic–Pituitary–Adrenal Axis

An Initial, Three-Day-Long Treatment with Alcohol Induces a Long-Lasting Phenomenon of Selective Tolerance in the Activity of the Rat Hypothalamic–Pituitary–Adrenal Axis

Relapse to smoking during unaided cessation: clinical, cognitive and motivational predictors

Smoking, reward responsiveness, and response inhibition: tests of an incentive motivational model

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