The data derived from studies using the reinstatement model suggest that the neuronal events that mediate drug-, cue- and stress-induced reinstatement of drug seeking are not identical, that the mechanisms underlying drug-induced reinstatement are to some degree different from those mediating drug discrimination or reward, and that the duration of the withdrawal period following cocaine and heroin self-administration has a profound effect on reinstatement induced by drug cues and stress. Finally, there appears to be a good correspondence between the events that induce reinstatement in laboratory animals and those that provoke relapse in humans.

Impulsive behaviors are closely linked to drug use and abuse, both as contributors to use and as consequences of use. Trait impulsivity is an important determinant of drug use during development, and in adults momentary ‘state’ increases in impulsive behavior may increase the likelihood of drug use, especially in individuals attempting to abstain. Conversely, acute and chronic effects of drug use may increase impulsive behaviors, which may in turn facilitate further drug use. However, these effects depend on the behavioral measure used to assess impulsivity. This article reviews data from controlled studies investigating different measures of impulsive behaviors, including delay discounting, behavioral inhibition and a newly proposed measure of inattention. Our findings support the hypothesis that drugs of abuse alter performance across independent behavioral measures of impulsivity. The findings lay the groundwork for studying the cognitive and neurobiological substrates of impulsivity, and for future studies on the role of impulsive behavior as both facilitator and a result of drug use.

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Non-contingent "priming" drug injections and conditioned stimuli associated with drug injections led to reinstatement of responding after a period of extinction. Rats implanted with intravenous catheters were trained to self-administer cocaine 1 mg/kg/injection), and then given daily test sessions consisting of a period of self-administration followed by extinction conditions. Test drug injections or conditioned stimuli were presented during extinction and the latency to the first response and the total number of responses following the treatment were measured. Cocaine injections of 0.5, 1.0, and 2.0 mg/kg restored responding during extinction, regardless of the duration of the extinction period (between 10 min and 180 min) since drug self-administration. Amphetamine, apomorphine, and morphine but not ethanol, heroin, or methohexital reinstated previously cocaine-reinforced responding. Amphetamine, cocaine, and morphine did not increase responding in animals trained to bar press only for food reinforcement, suggesting that the reinstatement effect is specific to drug-reinforced responses. The statement effect is specific to drug-reinforced responses. The final experiment showed that a tone that had been paired with drug infusions acquired a statistically significant tendency to facilitate responding when tested during extinction but this effect disappeared after the first test presentation of the tone.

Context Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse. Objective To prospectively assess the relationship of acute alcohol responses to future binge drinking. Design Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses. Setting Participants recruited from the community. Participants High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n=104) and light drinker controls (n=86). Intervention We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520). Main Outcome Measures Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Time-line Follow-Back, Drinker Inventory of Consequences–Recent, and DSM-IV alcohol abuse and dependence. Results Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence. Conclusions The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems. Trial Registration clinicaltrials.gov Identifier: NCT00961792

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation leveldependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.

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This study investigated the acute effects of D 9 -tetrahydrocannabinol (THC) on four behavioral measures of impulsivity in recreational marijuana users. Although impulsive behavior has been studied using several different measures of impulsivity, few studies have utilized more than one of these measures on a single cohort. In this study, 37 healthy men and women participated in three sessions, in which they received capsules containing placebo, 7.5, or 15 mg THC in randomized order under double-blind conditions. Subjects were tested on the following four tasks: the Stop task, which measures the ability to inhibit a prepotent motor response; a Go/no-go task; a Delay discounting task, which measures the value of delayed or uncertain reinforcers; and a time estimation task, which measures alterations in time perception through a time reproduction procedure. Subjects also completed mood questionnaires and general measures of performance. THC produced its expected effects on subjective measures including increases in ARCI euphoria and marijuana scales. THC increased impulsive responding on the Stop task but did not affect performance on either the Go/no-go or Delay or Probability discounting tasks. On the time reproduction task, THC increased estimates of the duration of short intervals while not affecting estimates of longer intervals. There were no significant correlations between the four tasks either before or after drug administration. These results suggest that THC may increase certain forms of impulsive behavior while not affecting other impulsive behaviors. The dissociations between the four measures of impulsivity suggest that impulsivity is an assemblage of distinct components rather than a unitary process.