Designing studies of drug conditioning in humans. Psychopharmacology, 106, 143-153

Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-6178.
Psychopharmacology (Impact Factor: 3.88). 02/1992; 106(2):143-53. DOI: 10.1007/BF02801965
Source: PubMed

ABSTRACT There has been much recent interest in the possibility that signals for drug use in humans acquire the ability to evoke classically conditioned (learned) states which motivate drug taking. Much data now suggest that cues paired with drug use come to elicit physiological responses and subjective reports of drug-related feelings like craving and withdrawal. However, the designs employed do not permit the conclusion that the observed responding results from classical conditioning. Studies which look directly at conditioning in the laboratory by pairing neutral stimuli with drug administration have not provided appropriate controls for unlearned effects such as sensitization or pseudo-conditioning. Similarly, studies which assess responding to cues thought to signal drug use in the natural environment (e.g., the sight of someone injecting heroin) have not adequately assessed whether such cues have unconditioned (unlearned) effects. Determining whether responding to drug-related cues results from classical conditioning has important implications for the development of drug treatments. Consequently, the purpose of the present review is to outline a set of criteria for determining that responses to drug-related stimuli in humans are learned. Existing studies are reviewed in light of these criteria and paradigms for further work are suggested.

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Available from: Steven J Robbins, Sep 27, 2015
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    • "Both arousal-control and cross-over response designs (Robbins and Ehrman 1992) were utilized to examine the specificity of reactivity ratings for substance cues. Participants were grouped based on their history of substance use prior to their incarceration using information collected during clinical interviews used for admittance to the RDAP (see Methods section for details). "
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    ABSTRACT: Background: Research on reactivity to alcohol and drug cues has either ignored affective state altogether or has focused rather narrowly on the role of negative affect in craving. Moreover, until recently, the relevant analyses of affect and craving have rarely addressed the ambivalence often associated with craving itself. The current study investigated how both negative and positive affect moderate approach and avoidance inclinations associated with cue-elicited craving in a clinical sample diagnosed with substance use disorders. Methods: One hundred forty-four patients (age range of 18-65, mean 42.0; n=92 males) were recruited from an inpatient detoxification unit for substance abuse. Participants completed a baseline assessment of both positive and negative affect prior to completing a cue-reactivity paradigm for which they provided self-report ratings of inclinations to approach (use) and avoid (not use) alcohol, cigarettes, and non-psychoactive control substances (food and beverages). Results: Participants with elevated negative affect reported significantly higher approach ratings for cigarette and alcohol cues, whereas those high in positive affect showed significantly higher levels of avoidance inclinations for both alcohol and cigarette cues and also significantly lower approach ratings for alcohol cues, all relative to control cues. Conclusions: Results for negative affect are consistent with previous cue reactivity research, whereas results for positive affect are unique and call attention to its clinical potential for attenuating approach inclinations to substance use cues. Further, positive affect was related to both approach and avoidance inclinations, underscoring the utility of a multidimensional conceptualization of craving in the analysis.
    Addictive behaviors 12/2012; 38(4):1970-1979. DOI:10.1016/j.addbeh.2012.12.003 · 2.76 Impact Factor
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    • "In human drug users, drug-paired cues have been reported to trigger cravings that are thought to motivate increased drug consumption or produce a relapse of drug selfadministration even after a prolonged period of abstinence (Childress et al., 1987, 1988; O'Brien et al., 1992; Robbins and Ehrman, 1992). This phenomenon has also been demonstrated in the animal laboratory where the presentation of drug-paired cues has been shown to reinstate drug-reinforced responding that had been weakened through a period of non-reinforced extinction responding (Crombag et al., 2008; Shaham et al., 2003). "
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    ABSTRACT: Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-h prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for 1 or 3 weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior ("retreats") regarding goal-box entry, reflecting cocaine's dual positive+negative effects. Once established, retreat behaviors persisted over the course of 1 or 3 weeks days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli.
    Pharmacology Biochemistry and Behavior 01/2012; 100(3):458-63. DOI:10.1016/j.pbb.2011.10.006 · 2.78 Impact Factor
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    • "In general, the results of these studies using physiological measures of motivational valence are in line with the prediction of incentive theories. However, they are silent about whether the reactivity evoked by naturalistic cues is indeed the result of conditioning (Robbins and Ehrman 1992). Direct evidence for this assumption comes from studies in which conditioning of previously neutral stimuli actually took place. "
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    ABSTRACT: Smoking cues are theorized to be conditioned stimuli (CSs) formed by repeated pairing with drug. Smoking paraphernalia can elicit subjective and physiological responses in smokers, indicative of positive affect and motivation to consume. Although these responses are probably the result of conditioning, direct evidence from human conditioning studies with physiological measures of motivational valence is rare. The present study investigated the motivational properties of experimentally conditioned cues for smoking. Thirty-nine smokers completed a differential conditioning protocol. Abstract pictures were used as CSs and single puffs on a cigarette as unconditioned stimulus (US). Skin conductance responses and facial electromyography of the zygomatic, corrugator, and orbicularis oris muscles were measured during conditioning. The conditioned cue for smoking (CS+) elicited stronger skin conductance responses and more activity of the zygomatic and orbicularis oris muscles than the CS-. These results support the notion that through pairing with smoking, neutral stimuli acquire the ability to elicit preparatory physiological responses, which are assumed to play an important role in the maintenance of addiction and relapse in the natural environment.
    Psychopharmacology 02/2011; 213(4):781-9. DOI:10.1007/s00213-010-2033-2 · 3.88 Impact Factor
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