Impulsive choice as a predictor of acquisition of IV cocaine self- administration and reinstatement of cocaine-seeking behavior in male and female rats.

Drug abuse and impulsive choice are related in humans. In female rats, impulsive choice predicted the rate of acquisition of IV cocaine self-administration. The objectives of the present experiments were to: (a) compare impulsive choice in males and females, (b) extend previous research on impulsive choice and acquisition of cocaine self-administration to males, and (c) compare males and females during maintenance, extinction, and reinstatement of cocaine-seeking behavior. Male and female rats were trained on an adjusting delay task in which a response on one of two levers yielded one food pellet immediately, and a response on the other resulted in three pellets after an adjusting delay that decreased after responses on the immediate lever and increased after responses on the delay lever. A mean adjusted delay (MAD) was used as the quantitative measure of impulsivity. In Experiment 1, MADs were analyzed for sex differences. In Experiment 2, acquisition of cocaine self-administration was examined in rats selected for high (HiI; MADs ≤9 seconds) or low (LoI; MADs ≥13 seconds) impulsivity. In Experiment 3, HiI and LoI groups were compared on maintenance and extinction of cocaine self-administration and cocaine-primed reinstatement of drug-seeking behavior. There were no sex differences in impulsive choice; however, HiI male and female rats acquired cocaine self-administration faster than their LoI counterparts. LoI females responded more on a cocaine-associated lever during maintenance and extinction than HiI females, but HiI females showed greater reinstatement of cocaine-seeking behavior than all other groups at the highest dose tested (15 mg/kg). Thus, individual differences in impulsive choice were associated with differences in cocaine-seeking behavior. Impulsive choice and sex may be additive vulnerability factors in certain phases of drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay discounting of cocaine by rhesus monkeys.

The present, subjective value of a reinforcer typically decreases as a function of the delay to its receipt, a phenomenon termed delay discounting. Delay discounting, which is assumed to reflect impulsivity, is hypothesized to play an important role in drug abuse. The present study examined delay discounting of cocaine injections by rhesus monkeys. Subjects were studied on a discrete-trials task in which they chose between 2 doses of cocaine: a smaller, immediate dose and a larger, delayed dose. The immediate dose varied between 0.012 and 0.4 mg/kg/injection, whereas the delayed dose was always 0.2 mg/kg/injection and was delivered after a delay that varied between 0 and 300 s in different conditions. At each delay, the point at which a monkey chose the immediate and delayed doses equally often (i.e., the ED50) provided a measure of the present, subjective value of the delayed dose. Dose-response functions for the immediate dose shifted to the left as delay increased. The amount of the immediate dose predicted to be equal in subjective value to the delayed dose decreased as a function of the delay, and hyperbolic discounting functions provided good fits to the data (median R2 = .86). The current approach may provide the basis for an animal model of the effect of delay on the subjective value of drugs of abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine exposure causes long-term increases in impulsive choice.

In this study, the authors examined the long-term effects of prior exposure to cocaine on a delay-discounting task commonly used to measure impulsive choice. Male Long-Evans rats received daily intraperitoneal injections of 30 mg/kg cocaine HCl or saline for 14 days. Following 3 weeks of withdrawal, rats began training. On each trial, rats were given a choice between 2 levers. A press on 1 lever resulted in immediate delivery of a single 45-mg food pellet, and a press on the other resulted in delivery of 4 pellets after a delay period. Impulsive choice was defined as preference for the small immediate over the large delayed reward. Three months after treatment, cocaine-exposed rats displayed increased impulsive choice behavior. They also showed less anticipatory responding (entries into the food trough) during the delays prior to reward delivery, indicating that the enhanced impulsive choice in these rats may be related to deficits in bridging the delay between response and reward. These data demonstrate that cocaine exposure can cause enduring increases in impulsive choice behavior, consistent with observations in human subjects with drug addictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the nucleus accumbens core in impulsive choice, timing, and reward processing.

The present series of experiments aimed to pinpoint the source of nucleus accumbens core (AcbC) effects on delay discounting. Rats were trained with an impulsive choice procedure between an adjusting smaller sooner reward and a fixed larger later reward. The AcbC-lesioned rats produced appropriate choice behavior when the reward magnitude was equal. An increase in reward magnitude resulted in a failure to increase preference for the larger later reward in the AcbC-lesioned rats, whereas a decrease in the larger later reward duration resulted in normal alterations in choice behavior in AcbC-lesioned rats. Subsequent experiments with a peak timing (Experiments 2 and 3) and a behavioral contrast (Experiment 4) indicated that the AcbC-lesioned rats suffered from decreased incentive motivation during changes in reward magnitude (Experiments 2 and 4) and when expected rewards were omitted (Experiments 2 and 3), but displayed intact anticipatory timing of reward delays (Experiments 2 and 3). The results indicate that the nucleus accumbens core is critical for determining the incentive value of rewards, but does not participate in the timing of reward delays. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laboratory and self-report assessments of impulsive behavior in adolescent daily smokers and nonsmokers.

This research compared adolescent daily smokers (n = 25) and nonsmokers (n = 26) on different measures of impulsivity. Assessments included question-based measures of delay (DDQ) and probability (PDQ) discounting, a measure of behavioral disinhibition (go-stop task), and a self-report measure of impulsivity (Barratt Impulsiveness Scale-Adolescent). Adolescent smokers were more impulsive on the DDQ and Barratt Impulsiveness Scale--Adolescent but not on the PDQ or the go-stop task. However, there was a significant interaction between smoking status and gender on the go-stop task, with male smokers performing less impulsively on this measure than male nonsmokers--an effect not observed with the female adolescents. These findings indicate that adolescents who smoke cigarettes are more impulsive with respect to some, but not all, types of impulsivity than are adolescents who do not smoke. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disinhibitory psychopathology and delay discounting in alcohol dependence: Personality and cognitive correlates.

Increased discounting of delayed rewards may reflect a decision bias that contributes to excessive use of alcohol and more generally, to an impulsive, disinhibitory predisposition that is characterized by a preference for immediate over long-term rewards. The current study examined the association between delay discounting of rewards and the covariation among several types of disinhibitory problems that are often comorbid with alcohol dependence (AD). Lifetime problems with alcohol, marijuana, other drugs, childhood conduct disorder, and adult antisocial behavior were assessed in a sample of 426 young adults, 257 of whom had a lifetime diagnosis of AD. Higher delay discounting rates were associated with the covariation among all domains of disinhibitory problems and were not uniquely associated with any one domain. Higher delay discounting rates also were associated with lower intelligence, lower working memory capacity, and higher trait impulsivity. The results suggest that increased delay discounting of rewards may reflect aspects of a general vulnerability to externalizing, disinhibitory disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain differences in patterns of drug-intake during prolonged access to cocaine self-administration.

The current study examined possible interactions between genetic factors and prolonged drug access by testing the Fischer (F344), Lewis (LEW), and Wistar rat strains in a prolonged access cocaine self-administration (SA) procedure. Before prolonged access, the strains did not differ in breakpoints for food or cocaine with progressive ratio (PR) testing. The LEW and Wistar rats acquired cocaine SA faster than the F344s. With prolonged access to cocaine SA, the LEW and Wistar rats showed comparable within-session patterns that were higher at the outset of each session and decreased to a stable baseline. Alternatively, the F344 rats began sessions with lower intake and increased their rate of intake during the session. The F344 and Wistar rats took more drug per session than the LEW rats but did not differ from each other. Following prolonged access, the strains did not differ in breakpoints for food, but the Wistar rats had higher breakpoints for cocaine than the F344 rats. Possible underpinnings for the observed strain differences are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impulsivity and rapid discounting of delayed hypothetical rewards in cocaine-dependent individuals.

In this study, crack/cocaine-dependent (CD) and non-drug-using matched control (MC) participants were presented with hypothetical immediate and delayed rewards, with 16 delay conditions ranging from 5 min to 25 years. All participants were presented with hypothetical monetary rewards; however, the CD group was also presented with hypothetical crack/ cocaine rewards. The objective value of the rewards ranged from $1 to $1,000. Hyperbolic discounting functions provided a good fit of the data. The CD group discounted monetary rewards at a higher rate than the MC group did, and the CD group discounted crack/cocaine rewards at a higher rate than it did monetary rewards. Moreover, scores on self-report measures indicated greater impulsivity in the CD group when compared with the MC group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dimensions of impulsive behavior in adolescent smokers and nonsmokers.

Robust associations have been identified between impulsive personality characteristics and cigarette smoking during adolescents, indicating that impulsive behavior may play an important role in the initiation of cigarette smoking. The present study extended this research by using laboratory behavioral assessments to explore relationships between three specific dimensions of impulsive behavior (impulsive decision-making, inattention, and disinhibition) and adolescent cigarette smoking. Participants were male and female adolescent smokers (n = 50) and nonsmokers (n = 50). Adolescent smokers were more impulsive on a measure of decision-making; however, there were significant smoking status by gender interaction effects for impulsive inattention and disinhibition. Male smokers were most impulsive on the measure of inattention, but male smokers were least impulsive on the measure of disinhibition. Correlations between biomarkers of smoking and impulsive inattention and disinhibition were found for females but not males. The current findings, coupled with previous findings (Reynolds et al., 2007), indicate there may be robust gender difference in associations between certain types of impulsive behavior and cigarette smoking during adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dimensions of impulsive behavior in adolescents: Laboratory behavioral assessments.

Impulsivity is a multifaceted construct that defines a range of maladaptive behavioral styles. The present research aimed to identify different dimensions of impulsive behavior in adolescents from a battery of laboratory behavioral assessments. In one analysis, correlations were examined between two self report and seven laboratory behavioral measures of impulsivity. The correlation between the two self report measures was high compared to correlations between the self report and laboratory behavioral measures. In a second analysis, a principal components analysis was performed with just the laboratory behavioral measures. Three behavioral dimensions were identified--"impulsive decision-making", "impulsive inattention", and "impulsive disinhibition". These dimensions were further evaluated using the same sample with a confirmatory factor analysis, which did support the hypothesis that these are significant and independent dimensions of impulsivity. This research indicates there are at least three separate subtypes of impulsive behavior when using laboratory behavioral assessments with adolescent participants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of acquisition training schedule on extinction and reinstatement of cocaine self-administration in male rats.

Partial reinforcement is known to increase resistance to extinction (Rn) relative to training with continuous reinforcement. This phenomenon, referred to as the partial reinforcement extinction effect, is one of the most robust in learning and conditioning studies. Experiment 1 investigated manipulations known to affect the partial reinforcement extinction effect and determined their possible relevance for drug use patterns. Male rats received intravenous cocaine self-administration training under partial reinforcement (FR-10) training or continuous reinforcement (FR-1) conditions with either a low (0.25 mg/kg infusion) or a high cocaine dose (1.00 mg/kg infusion). Animals were placed on an extinction (recurrent nonreward) schedule for 10 days (1-hr sessions) prior to being tested for cue-induced reinstatement (single 2-hr session). Experiment 2 involved acquisition of cocaine self-administration under FR-1 conditions of short training (15 days) or extended training (30 days) with a low dose (0.25 mg/kg infusion) or a medium dose (0.50 mg/kg infusion) of cocaine reward prior to extinction or reinstatement. Experiment 1 showed that rats trained with FR-10-high dose outcomes exhibited greater Rn than the remaining groups. Additionally, FR-10-high dose and FR-10-low dose rats were more likely to return to active drug seeking during the reinstatement test. In Experiment 2, rats trained under FR-1-medium dose conditions were more persistent during extinction following short acquisition training than comparable rats experiencing extended acquisition training. The reinstatement test was conducted following extinction, in which it was observed that overtraining under FR-1-medium dose reward schedules resulted in a decrease in the tendency to return to active drug seeking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A multivariate assessment of individual differences in sensation seeking and impulsivity as predictors of amphetamine self-administration and prefrontal dopamine function in rats.

Drug abuse vulnerability has been linked to sensation seeking (behaviors likely to produce rewards) and impulsivity (behaviors occurring without foresight). Since previous preclinical work has been limited primarily to using single tasks as predictor variables, the present study determined if measuring multiple tasks of sensation seeking and impulsivity would be useful in predicting amphetamine self-administration in rats. Multiple tasks were also used as predictor variables of dopamine transporter function in the medial prefrontal and orbitofrontal cortexes, as these neural systems have been implicated in sensation seeking and impulsivity. Rats were tested on six behavioral tasks as predictor variables to evaluate sensation seeking (locomotor activity, novelty place preference, and sucrose reinforcement on a progressive ratio schedule) and impulsivity (delay discounting, cued go/no-go, and passive avoidance), followed by d-amphetamine self-administration (0.0056–0.1 mg/kg infusion) and kinetic analysis of dopamine transporter function as outcome variables. The combination of these predictor variables into a multivariate approach failed to yield any clear relationship among predictor and outcome measures. Using multivariate approaches to understand the relation between individual predictor and outcome variables in preclinical models may be hindered by alterations in behavior due to training and thus, the relation between various individual differences in behavior and drug self-administration may be better assessed using a univariate approach in which a only a single task is used as the predictor variable. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Differences in impulsivity and risk-taking propensity between primary users of crack cocaine and primary users of heroin in a residential substance-use program.

Crack cocaine use is more associated with impulsivity and a propensity to take risks than heroin use, yet no studies have examined this relationship in the absence of acute drug effects. The current study examined impulsivity (using the Delay Discounting Task) and risk-taking propensity (using the Balloon Analogue Risk Task) across independent groups of primary crack cocaine users with minimal heroin use (n=16) and primary heroin users with minimal crack cocaine use (n=11) in residential treatment, with all participants drug abstinent during participation. Crack cocaine users evidenced greater levels of impulsivity and risk-taking propensity, with only the difference in impulsivity persisting after controlling for age and gender. These data hold potential theoretical importance in understanding differences between crack cocaine and heroin users, as the findings cannot be attributed solely to acute pharmacological drug effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Risk factors in the relationship between gender and crack/cocaine.

Female inner-city substance users evidence greater crack/cocaine use and are more likely to be dependent on this drug than on any other drug. Additionally, female inner-city substance users evidence greater crack/cocaine use and are more likely to be dependent on this drug than their male counterparts, despite no consistent difference demonstrated in use and dependence across other drugs. Because no published work has empirically examined the factors underlying this link between females and crack/cocaine, the current study examined the role of theoretically relevant personality and environmental variables. Among 152 (37% female) individuals in a residential substance-use treatment program, females evidenced greater use of crack/cocaine (current and lifetime heaviest) and were significantly more likely to evidence crack/cocaine dependence than their male counterparts. In contrast, no gender differences were found for any other substance across alcohol, cannabis, and hallucinogens (including PCP). Surprisingly, females were more impulsive than their male counterparts, with impulsivity serving as a risk factor in the relationship between gender and crack/cocaine dependence and lifetime heaviest use. Females also evidenced higher levels of negative emotionality and childhood abuse, but neither variable served as a risk factor in the relationship between gender and crack/cocaine dependence or use. Limitations and future directions are discussed, including the need for further exploration of impulsivity across its various dimensions as well as the inclusion of additional variables such as social context variables to account more fully for this complex link between gender and crack/cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay discounting is associated with treatment response among cocaine-dependent outpatients.

Delay discounting (DD) describes the rate at which reinforcers lose value as the temporal delay to their receipt increases. Steeper discounting has been positively associated with vulnerability to substance use disorders, including cocaine use disorders. In the present study, we examined whether DD of hypothetical monetary reinforcers is associated with the duration of cocaine abstinence achieved among cocaine-dependent outpatients. Participants were 36 adults who were participating in a randomized controlled trial examining the efficacy of voucher-based contingency management (CM) using low-magnitude (N = 18) or high-magnitude (N = 18) voucher monetary values. DD was associated with the number of continuous weeks of cocaine abstinence achieved, even after adjusting for treatment condition during the initial 12-week, t(33) = 2.48, p = .045 and entire recommended 24-week of treatment, t(33) = 2.40, p = .022. Participants who exhibited steeper discounting functions achieved shorter periods of abstinence in the Low-magnitude voucher condition (12-week: t(16) = 2.48, p = .025; 24-week: t(16) = 2.68, p = .017), but not in the High-magnitude voucher condition (12-week: t(16) = 0.51, p = .618; 24-week: t(16) = 1.08, p = .298), although the interaction between DD and treatment condition was not significant (12-week: t(32) = ?1.12, p = .271; 24-week: t(32) = ?0.37, p = .712). These results provide further evidence on associations between DD and treatment response and extend those observations to a new clinical population (i.e., cocaine-dependent outpatients), while also suggesting that a more intensive intervention like the High-magnitude CM condition may diminish this negative relationship between DD and treatment response. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Discounting of past outcomes.

Drug use, abuse, and addiction are common behavioral manifestations of impulsiveness. A useful and popular laboratory analogue of impulsiveness is temporal discounting. Temporal discounting refers to the reduction in the present, subjective value of outcomes that are temporally distant in the future. The extensive literature on temporal discounting indicates hyperbolic discounting, the magnitude effect, and the sign effect. It is possible that the same principles may apply to other dimensions of psychological distance, including past temporal distance. The purpose of the present study was to examine the possibility that outcomes in the past are discounted hyperbolically and at a similar rate to outcomes in the future. The magnitude and sign effects were also examined in past discounting. Indifference points of college students were determined from a paper-and-pencil questionnaire of future and past discounting. The results demonstrate that humans discount temporally distant past outcomes similarly to future outcomes. Discounting of the future and past are qualitatively and quantitatively similar; discounting of past outcomes is orderly, hyperbolic, and consistent with most empirical observations from studies of future discounting, including the magnitude and sign effects. The present study indicates that the discounting of past outcomes is a quantifiable phenomenon, and the results are similar to observations from the established future-discounting literature. Past discounting may be of use in the study of drug-dependent and other impulsive populations. Implications of a relationship between future and past discounting are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of sex, estrous cycle, and drug-onset age on cocaine self-administration in rats (Rattus norvegicus).

The influence of sex, phase of the estrous cycle, and age of drug onset on cocaine self-administration was examined. Adult male, adult female, and adolescent male rats (Rattus norvegicus) were evaluated using low fixed-ratio (FR) schedules of drug delivery with a single fixed cocaine unit dose or a range of cocaine unit doses with a single FR schedule. Sex differences in adults were observed for mg/kg consumption of the 3.0-mg/kg unit dose, with consumption being significantly less in estrus females than in males. Over the estrous cycle, mg/kg consumption of this unit dose was significantly less during estrus than during metestrus-diestrus. Differences due to age of drug onset were also observed, with mg/kg consumption of the 3.0-mg/kg unit dose being significantly less in adolescent males than adult males or adult females during metestrus-diestrus. In contrast, these various groups did not have significantly different mg/kg intakes of cocaine unit doses     

Role of impulsivity in the relationship between depression and alcohol problems among emerging adult college drinkers.

Depression is common among college students and higher levels of depression are associated with greater alcohol-related problems. However, depression is frequently not found to be directly associated with more alcohol use. This study examined whether various aspects of impulsivity (negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and delay discounting) and drinking to cope with negative affect help to account for the relationship between depression and alcohol problems among emerging adult college drinkers who reported at least a minimal level of depressive symptoms. In this cross-sectional study, 143 emerging adult (between 18 and 25 years old) female (69.9%, n = 100) and male (30.1%, n = 43) college drinkers with at least minimal depressive symptoms completed measures of depression, alcohol use and problems, drinking to cope, and impulsivity. A multiple mediation analysis revealed that only negative urgency and drinking to cope partially mediated the depression-alcohol problems relationship. Moderated mediation analyses revealed that impulsivity-related constructs did not significantly interact with drinking to cope to increase alcohol problems. It appears that alcohol use is particularly problematic for students with elevated depression, and this is partly attributable to depression's association with negative urgency, in addition to its association with drinking to cope. Our findings suggest that students who suffer from depression may engage in problematic drinking behavior in part because negative affect is detrimental to their short-term impulse control and decision making, independent of maladaptive attempts to regulate affect through drinking to cope. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Diazepam impairs behavioral inhibition but not delay discounting or risk taking in healthy adults.

There are reports that diazepam can increase, decrease, or have no effect on measures of impulsive behavior, which may be related, in part, to differences among the tasks used to measure impulsivity. This study examined the effects of a relatively high dose of diazepam (20 mg) on 5 measures of impulsive behavior in healthy adult men and women. Volunteers (N = 18) participated in a 2-session double-blind randomized design in which they received 20 mg diazepam or placebo. One hour after ingesting the capsule, participants completed mood questionnaires and several impulsivity tasks to measure subtypes of impulsive behavior, including behavioral inhibition, delay and probability discounting, and risk taking. Diazepam impaired behavioral inhibition but had no effect on measures of discounting or risk taking. These results are discussed in the context of other recent findings suggesting that different behavioral indices of impulsivity are dissociable and governed by separate underlying mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional neuroimaging of intertemporal choice models: A review.

People often forsake a larger reward later for a smaller reward sooner. The process of devaluing the larger, later prize is called temporal discounting or delay discounting, which lies at the core of intertemporal choice. Here, we describe the methodology and findings of research on the mechanisms of intertemporal choice, with a focus on those that utilize functional MRI (fMRI). We consider the neural bases for the most common economic models of intertemporal choice and examine whether these models require neural processes that are common or distinct across types of decision making. Considered as a whole, current research points to potentially distinct contributions from brain systems associated with valuation and with prospective thought, which may be reflected in separable foci in posterior cingulate cortex. Based on open questions in the field, we suggest two core goals for future research: identifying aspects of valuation that are unique to intertemporal choice and evaluating direct or indirect interactions between delay and prize magnitude. (PsycINFO Database Record (c) 2010 APA, all rights reserved)