Cocaine-related Stimuli Research Articles

Attentional biases in abstinent patients with cocaine use disorder: rapid orienting or delayed disengagement?

Addiction-related attentional biases may play a central role in the development and maintenance of drug-seeking and drug-taking behaviors. However, evidence in cocaine dependence is limited and mixed. This study examined the time course and component processes of attentional biases for cocaine-related cues in a sample of 47 outpatients (38 men) with cocaine use disorder (CUD) with varying durations of current abstinence. Reaction times in a visual dot-probe task with two picture exposure durations -500 ms, to assess initial stages of attention, and 2,000 ms, to assess maintained attention- were recorded. We found faster responses to probes replacing cocaine-related vs. matched control pictures in the 500 ms but not in the 2,000 ms condition, indicative of early but not late attentional biases for cocaine cues in abstinent patients with CUD. Further comparisons with a neutral baseline revealed that it was not due to rapid orienting but to delayed disengagement from cocaine-related pictures, being this effect greater the longer the period of current abstinence. Consistent with the incentive-sensitization theory, these data suggest that cocaine-related stimuli maintain the capacity to hold spatial attention in abstinent patients with CUD, even after months of abstinence, highlighting the relevance of carrying out stimulus control to avoid relapses.

The BDNF Val66Met Polymorphism Moderates the Relationship Between Posttraumatic Stress Disorder and Trauma Script-evoked Attentional Bias to Cocaine Cues Among Patients with Cocaine Dependence

There is extensive variability in cocaine-related attentional bias (AB) following trauma script exposure among cocaine-dependent (CD) patients with posttraumatic stress disorder (PTSD). Therefore, research is needed to identify the specific PTSD-CD patients most likely to exhibit an AB to cocaine cues. A common polymorphism in brain-derived neurotrophic factor (BDNF), Val66met, is associated with risk for stimulant addiction, and thus, was examined as a moderator of the association between PTSD and cocaine-related AB following trauma script exposure in this study. Adult CD patients with (n = 17) and without (n = 28) PTSD were exposed to a personalized trauma script, followed by a visual dot-probe task assessing cocaine-related AB. Task response times were used to examine traditionally calculated AB scores, as well as trial level bias scores (TL-BS) that more accurately model the temporal dynamics of AB. PTSD-CD patients homozygous for the BDNF Val/Val genotype exhibited greater bias for attending to cocaine-related stimuli following trauma script exposure than those carrying the Met allele. The PTSD by BDNF interaction did not predict response time variability on trials for which only neutral stimuli were presented, thus increasing confidence that the observed effect is specific to cocaine-related stimuli. PTSD-CD patients homozygous for the BDNF Val/Val genotype may be at particularly high risk for negative clinical outcomes (e.g., relapse, treatment dropout) as a function of prolonged attentional engagement with cocaine cues when exposed to trauma reminders.

Attentional bias toward alcohol stimuli as a predictor of treatment retention in cocaine dependence and alcohol user patients

BackgroundAttentional bias towards substance-related stimuli has shown to be involved in the development and maintenance of cocaine dependence. The relationship between alcohol use and cocaine dependence shown in literature justify the need of study these two substances jointly. MethodsThis paper analyzes patterns of attentional bias in 71 patients with cocaine dependence and compares these patterns according to whether occasional or problematic concurrent alcohol use is taken into account. It also analyzes whether attentional bias towards alcohol and cocaine-related stimuli predicts treatment retention. Attentional bias was evaluated with a visual probe task between 15 and 20days after admission to treatment. Treatment status was recorded at a three-month follow-up. Severity of dependence and cocaine and alcohol craving were also measured. ResultsResults show that patients with cocaine dependence and problematic alcohol use show a pattern of approach towards alcohol stimuli (M=8.32, SD=27.01). In contrast, patients with cocaine dependence with occasional consumption of alcohol exhibit a pattern of avoidance of such stimuli (M=−7.23, SD=19.20) (t=2.79, p=0.007). Logistic regression indicates that alcohol attentional bias is the only variable with predictive capacity (OR=1.05, 95% CI=[1.01, 1.09]). It should also be noted that there is a pattern of avoidance of alcohol stimuli in patients who drop out of treatment. ConclusionThe results of this study suggest the need to delve into whether therapeutic strategies involving deeper emotional processing or avoidance strategies are more suitable for preventing relapse.

N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order

BackgroundDisrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. MethodsThe present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg). Fourteen individuals (N=14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. ResultsCocaine-cue attentional bias was greatest following administration of 0mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. ConclusionsThese results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues.

Impulsivity and Attentional Bias in Cocaine Dependence: Does Familial Substance Misuse Contribute to Neurobehavioral Performance?

The goal of the present study was to examine the relationship between family history of alcohol and illicit drug abuse and impulsivity in cocaine users and healthy controls. One hundred and thirty-five individuals recruited for a larger study (58 cocaine users and 77 healthy controls) with and without family history of substance misuse participated in the study. Individuals completed a computer-administered interview regarding family history of substance misuse and neurobehavioral measures of impulsivity and attentional bias. Family history of substance misuse was found to be associated with greater attentional bias to cocaine-related stimuli, regardless of personal drug use status (cocaine user versus healthy control). These findings suggest that drug cues may be more salient to first degree relatives of substance users. However, the nature of this relationship to genetic and/or environmental factors is unknown.

Cocaine-related stimuli impair inhibitory control in cocaine users following short stimulus onset asynchronies.

Cocaine users display a significant increase in inhibitory failures following cocaine-related images compared with neutral images in a modified cued Go/No-Go task, the Attentional Bias-Behavioral Activation (ABBA) task. The aim of this study was to demonstrate that stimulus onset asynchrony (SOA) impacts inhibitory failures on the ABBA task. A between-subjects experiment. An out-patient research unit in the United States. Ninety-one cocaine users recruited from the community. Participants were assigned to groups in which they saw either cocaine (n=46) or neutral (n=45) images as the go condition. Cues were presented for one of five SOAs (i.e. 100, 200, 300, 400 or 500 ms) before a go or no-go target was displayed. Participants in the cocaine go condition had a significantly higher proportion of inhibitory failures to no-go targets (F4,356=2.50, P=0.04) with significantly more inhibitory failures following all SOAs (P<0.05) than those in the neutral go condition. Within the cocaine go condition, significantly more inhibitory failures were observed following the 100 and 200 ms SOAs than after the 300, 400 or 500 ms SOAs (P<0.05). Cocaine-related stimuli appear to decrease inhibitory control in cocaine users at short (100 and 200 ms) stimulus onset asynchronies (SOAs: the amount of time between the start of one stimulus and the start of another stimulus), but not at longer (300, 400 and 500 ms) SOAs.

Fixation time is a sensitive measure of cocaine cue attentional bias

Attentional bias has been demonstrated to a variety of substances. Evidence suggests that fixation time is a more direct measure of attentional bias than response time. The aims of this experiment were to demonstrate that fixation time during the visual probe task is a sensitive and stable measure of cocaine cue attentional bias in cocaine-using adults compared to controls. A between-subject, repeated-measures experiment. An out-patient research unit. Fifteen cocaine using and 15 non-cocaine-using adults recruited from the community. Participants completed a visual probe task with eye tracking and a modified Stroop during two experimental sessions. A significant interaction between cue type and group (F = 13.5; P < 0.05) indicated that cocaine users, but not controls, displayed an attentional bias to cocaine-related images as measured by fixation time. There were no changes in the magnitude of attentional bias across sessions (F = 3.4; P > 0.05) and attentional bias correlated with self-reported life-time cocaine use (r = 0.64, P < 0.05). Response time on the visual probe (F = 1.1; P > 0.05) as well as on the modified Stroop (F = 0.1; P > 0.05) failed to detect an attentional bias. Fixation time on cocaine-related stimuli (propensity to remain focused on the stimulus) is a sensitive and stable measure of cocaine cue attentional bias in cocaine-using adults.

Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking

Hypothalamic orexin/hypocretin (Orx/Hcrt) peptides participate in the regulation of a wide range of physiological processes and are recruited by drugs of abuse. To advance our understanding of the potential of the Orx/Hcrt receptor-1 (Hcrt-r1) as a treatment target for cocaine addiction, the effect of SB334867 [N-(2-methyl-6-benzoxazolyl)-N'-1,5-n-aphthyridin-4-yl urea], a specific Hcrt-r1 antagonist, on reinstatement elicited by cocaine-associated stimuli versus stimuli associated with a highly palatable conventional reinforcer [sweetened condensed milk (SCM)] was tested. Two separate groups of male Wistar rats were trained to associate a discriminative stimulus (S⁺) with the response-contingent availability of cocaine (0.25 mg/0.1 ml/infusion) or SCM [2/1 (v/v)] and subjected to reinstatement tests following extinction of cocaine-reinforced or SCM-reinforced behavior, during which the reinforcers and S⁺ were withheld. Following extinction, presentation of the cocaine or SCM S⁺ produced comparable recovery of responding. Hcrt-r1 blockade by SB334867 (1-10 mg/kg, intraperitoneal) dose-dependently and selectively reversed conditioned reinstatement induced by cocaine-related stimuli, without interfering with reward seeking produced by the same stimulus when conditioned to SCM. The findings suggest an important role for Hcrt-r1 in appetitive behavior controlled by reward-related stimuli with selectivity for cocaine seeking and identify Hcrt-r1 as a potential treatment target for cocaine relapse prevention.

Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals

Addiction theories posit that drug-related cues maintain and contribute to drug use and relapse. Indeed, our recent study in cocaine-dependent patients demonstrated that subliminally presented cocaine-related stimuli activate reward neurocircuitry without being consciously perceived. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent drug-seeking behaviors. Using an equivalent paradigm, we tested whether cannabis cues activate reward neurocircuitry in treatment-seeking, cannabis-dependent individuals and whether activation was associated with relevant behavioral anchors: baseline cannabis craving (drug-seeking behavior) and duration of use (degree of conditioning). Twenty treatment-seeking, cannabis-dependent individuals (12 males) underwent event-related blood oxygen level-dependent functional magnetic resonance imaging during exposure to 33-ms cannabis, sexual, and aversive cues presented in a backward-masking paradigm. Drug use history and cannabis craving were assessed prior to imaging. Participants showed increased activity to backward-masked cannabis cues in regions supporting reward detection and interoception, including the left anterior insula, left ventral striatum/amygdala, and right ventral striatum. Cannabis cue-related activity in the bilateral insula and perigenual anterior cingulate cortex was positively associated with baseline cannabis craving, and cannabis cue-related activity in the medial orbitofrontal cortex was positively correlated with years of cannabis use. Neural responses to backward-masked sexual cues were similar to those observed during cannabis cue exposure, while activation to aversive cues was observed only in the left anterior insula and perigenual anterior cingulate cortex. These data highlight the sensitivity of the brain to subliminal reward signals and support hypotheses promoting a common pathway of appetitive motivation.

An investigation of the relationship between borderline personality disorder and cocaine-related attentional bias following trauma cue exposure: The moderating role of gender

Elevated rates of borderline personality disorder (BPD) have been found among individuals with substance use disorders (SUDs), especially cocaine-dependent patients. Evidence suggests that cocaine-dependent patients with BPD are at greater risk for negative clinical outcomes than cocaine-dependent patients without BPD and BPD-SUD patients dependent on other substances. Despite evidence that cocaine-dependent patients with BPD may be at particularly high risk for negative SUD outcomes, the mechanisms underlying this risk remain unclear. The present study sought to address this gap in the literature by examining cocaine-related attentional biases among cocaine-dependent patients with (n=22) and without (n=36) BPD. On separate days, participants listened to both a neutral and a personally-relevant emotionally evocative (i.e., trauma-related) script and then completed a dot-probe task with cocaine-related stimuli. Findings revealed a greater bias for attending to cocaine-related stimuli among male cocaine-dependent patients with (vs. without) BPD following the emotionally evocative script. Study findings suggest the possibility that cocaine use may have gender-specific functions among SUD patients with BPD, with men with BPD being more likely to use cocaine to decrease contextually induced emotional distress. The implications of our findings for informing future research on cocaine use among patients with BPD are discussed.

Enhanced Orbitofrontal Cortex Function and Lack of Attentional Bias to Cocaine Cues in Recreational Stimulant Users

Although cocaine is known to be a highly addictive drug, there appears to be a select subset of individuals who are able to use the substance recreationally without developing dependence. These individuals do not report experiencing feelings of craving for cocaine, an important distinction from dependent users. However, no prior studies have compared attentional bias with cocaine cues between these groups to confirm this difference. Additionally, previous investigations into cognitive abilities in these individuals have been conflicting, and no research has been conducted on the neurobiological processes underlying cognitive functioning in this group. This study administered the emotional cocaine-word Stroop to 27 recreational cocaine users, 50 stimulant-dependent individuals, and 52 healthy control participants during functional magnetic resonance imaging scanning. Behavioral and functional imaging results were compared between groups to assess attentional bias and cognitive effort to resist salient cocaine stimuli. Recreational users did not exhibit attentional bias to the cocaine words and did not differ from control subjects on task performance. Conversely, stimulant-dependent individuals were significantly more impaired on the task. Recreational participants also displayed a unique pattern of activation during performance, with significant underactivation in the orbitofrontal and anterior cingulate cortices compared with both dependent users and control subjects. The absence of bias to cocaine-related stimuli in recreational users indicates they do not share attentional preference for these words with dependent users. Their distinct pattern of activation suggests a decreased need for cognitive control due to diminished desire for the drug, potentially serving as a resilience factor against dependence.

Effects of escitalopram on attentional bias to cocaine-related stimuli and inhibitory control in cocaine-dependent subjects

Key characteristics of cocaine dependence include attentional bias to cocaine cues and impaired inhibitory control. Studies suggest that serotonin modulates both cocaine cue reactivity and inhibitory control. We investigated effects of the selective serotonin reuptake inhibitor escitalopram on cocaine cue reactivity and inhibitory processes in cocaine-dependent subjects. In a double-blind placebo-controlled design, cocaine-dependent subjects received placebo (n=12) or escitalopram (n=11; 10 mg on days 1-3, 20 mg on days 4-24 and 10 mg on days 25-28) orally, once daily for 4 weeks. The cocaine Stroop and immediate memory task (IMT) were administered at baseline, days 1, 4, 11, 18 and 25 after placebo or escitalopram initiation. There were no significant between-group differences in baseline performance on the cocaine Stroop task or the IMT. On day 1 (acute phase), escitalopram produced a significantly greater decrease from baseline than placebo in attentional bias measured by cocaine Stroop task 5 hours post-dose. No significant changes from baseline in attentional bias were observed on subsequent test days (chronic phase). Inhibitory control as measured by IMT commission error rate was not significantly different between two groups in either the acute or chronic phase. Consistent with preclinical data, serotonin-modulating drugs like escitalopram may have acute effects on cocaine cue reactivity in human cocaine users.

Measures of Attentional Bias and Relational Responding Are Associated with Behavioral Treatment Outcome for Cocaine Dependence

Background: Psychosocial interventions for substance dependence have demonstrated efficacy. However, the mechanisms by which specific intervention strategies exert their effect have not been clearly identified. Objective: This study investigated the prospective relationships between two psychological processes, an attentional bias toward cocaine stimuli and beliefs about the consequences of cocaine use, and treatment outcome. Method: Twenty-five cocaine-dependent participants enrolled in a 6-month outpatient treatment program that included voucher incentives for abstinence. All participants were asked to complete two implicit assessment procedures, a Drug Stroop protocol and an Implicit Relational Assessment Procedure (IRAP), as well as explicit measures of cocaine craving and the consequences of cocaine use, prior to beginning treatment. Pearson’s correlation coefficients tested the prospective relationships between treatment outcome and the implicit and explicit assessments. Results: Stronger implicit beliefs about the positive effects of cocaine use prior to treatment were associated with poorer treatment outcome when an escalating voucher-incentive program was in place. Further, an attentional bias for cocaine-related stimuli was associated with better treatment outcome when an escalating voucher-incentive program was removed. No association between cocaine use beliefs and treatment outcome was found when beliefs were measured with self-report instruments. Conclusions and scientific significance: These findings highlight the potential utility of performance-based measures for delineating the psychological mechanisms associated with variation in response to treatment for drug dependence.

Increased intra-individual reaction time variability in cocaine-dependent subjects: Role of cocaine-related cues

Neuroimaging data suggest that impaired performance on response inhibition and information processing tests in cocaine-dependent subjects is related to prefrontal and frontal cortical dysfunction and that dysfunction in these brain areas may underlie some aspects of cocaine addiction. In subjects with attention-deficit hyperactivity disorder and other psychiatric disorders, the Intra-Individual Reaction Time Variability (IIRTV) has been associated with frontal cortical dysfunction. In the present study, we evaluated IIRTV parameters in cocaine-dependent subjects vs. controls using a cocaine Stroop task. Fifty control and 123 cocaine-dependent subjects compiled from three studies completed a cocaine Stroop task. Standard deviation (SD) and coefficient of variation (CV) for reaction times (RT) were calculated for both trials with neutral and trials with cocaine-related words. The parameters mu, sigma, and tau were calculated using an ex-Gaussian analysis employed to characterize variability in RTs. The ex-Gaussian analysis divides the RTs into normal ( mu, sigma) and exponential ( tau) components. Using robust regression analysis, cocaine-dependent subjects showed greater SD, CV and Tau on trials with cocaine-related words compared to controls (p < 0.05). However, in trials with neutral words, there was no evidence of group differences in any IIRTV parameters (p > 0.05). The Wilcoxon matched-pairs signed-rank test showed that for cocaine-dependent subjects, both SD and tau were larger in trials with cocaine-related words than in trials with neutral words (p < 0.05). The observation that only cocaine-related words increased IIRTV in cocaine-dependent subjects suggests that cocaine-related stimuli might disrupt information processing subserved by prefrontal and frontal cortical circuits.

Relationship between attentional bias to cocaine-related stimuli and impulsivity in cocaine-dependent subjects

Background: Cocaine-dependent subjects show attentional bias to cocaine-related stimuli, increased impulsivity on questionnaires, and impaired inhibitory control (one component of impulsivity on behavioral tasks). However, the relationship between attentional bias, impulsivity, and inhibitory control in cocaine-dependent subjects is unknown. Objective: To investigate the relationship between attentional bias to cocaine-related stimuli, impulsivity, and inhibitory control in cocaine dependence. Methods: This study employed the cocaine Stroop task to measure attentional bias to cocaine-related stimuli, immediate memory task (IMT) to measure inhibitory control, and Barratt Impulsiveness Scale version 11 to measure impulsivity. Thirty-two controls and 37 cocaine-dependent subjects were recruited through newspaper advertisement. Results: Cocaine-dependent subjects had higher attentional bias to cocaine-related words, higher scores for Barratt Impulsiveness Scale, and higher commission error rate on the IMT than controls. The attentional bias was positively correlated with the commission error rate on the IMT in the cocaine-dependent subjects but not in control subjects. Conclusions: Cocaine-dependent subjects showed attentional bias to cocaine-related words, increased impulsivity, and poor inhibitory control compared with controls. The attentional bias was associated with inhibitory control in cocaine-dependent subjects but not in control subjects. Scientific Significance: Our findings suggest that cocaine-dependent subjects with poor inhibitory control may show higher attentional bias to cocaine-related words compared with controls and those with better inhibitory control.

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

Application of cocaine or exposure to cocaine-related stimuli induces widespread activation of the cortex in neuroimaging studies with human subjects. In accordance to these findings, it was reported in previous microdialysis experiments that cocaine increased serotonin (5-HT) and dopamine in various cortical brain areas. The present series of studies set out to investigate the functional role of the observed increases in 5-HT in the medial prefrontal cortex (mPFC), the entorhinal cortex (EC), and the occipital cortex (OccC) in the mediation of cocaine-induced conditioned place preference (CPP) and hyperactivity. To reduce 5-HTergic neurotransmission in circumscribed brain areas, bilateral local infusions of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), were made into the mPFC, EC, or OccC. Two weeks following surgery, cocaine-induced (10 mg/kg; i.p.) CPP was measured in an unbiased design. The 90% depletion of 5-HT in the mPFC significantly attenuated the preference for the cocaine-associated environment and the hyperlocomotor response to cocaine. A 61% depletion of 5-HT in the EC reduced conditioned place preference without modulation of hyperactivity, while a 78% 5-HT depletion of the OccC cortex had no effect on cocaine-induced CPP and hyperactivity. No lesion affected general activity, habituation learning, or visual stimulation-induced behavioral activation. These results indicate an important role of cortical 5-HT in the mediation of cocaine-induced CPP and specify the region-dependent contribution of a neurochemical response to cocaine-mediated behavior.

CLINICAL STUDY: Cocaine craving is associated with electrophysiological brain responses to cocaine‐related stimuli

Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.

Role of dopamine D1 receptors in the prefrontal dorsal agranular insular cortex in mediating cocaine self-administration in rats

Orbital/insular areas of the prefrontal cortex (PFC) are implicated in cocaine addiction. However, the role of dopamine D1 receptors in mediating cocaine self-administration in these sub-regions remains unknown. To define the role of the dorsal agranular insular (AId) sub-region of the PFC, we investigated the effects of D1 receptor manipulation on self-administration behavior maintained by cocaine and cocaine-related stimuli. Rats were trained to lever press for cocaine (1 mg/kg) under a fixed-interval 5-min (fixed-ratio 5:S) second-order schedule of reinforcement in the presence of conditioned light cues and contextual sound cues. Intra-AId infusions of vehicle, the D1-like receptor agonist SKF 81297 (0.1, 0.2, 0.4 microg/side) or the D1-like receptor antagonist SCH 23390 (1.0, 2.0, 4.0 microg/side), were administered prior to 1-h self-administration test sessions. Food-maintained responding under a second-order schedule was examined in separate rats to determine if pretreatment with D1 ligands produced general impairments in responding. Infusion of SKF 81297 (0.2 and 0.4 microg/side) reduced active lever responses during the first 30 min of 1-h test sessions, but did not influence cocaine intake. Infusion of 4.0 microg/side SCH 23390 reduced active lever responses and cocaine intake throughout the 1-h test sessions. Additionally, this dose of SCH 23390 disrupted food-maintained responding and intake. D1 receptor agonists and antagonists in the AId have diverse consequences and time courses of action. D1 receptor stimulation in the AId may reduce the motivating influence of cocaine-related stimuli on responding whereas D1 receptor blockade in this PFC sub-region produces global disruptions in behavior.

Attentional Bias Towards Cocaine-Related Stimuli: Relationship to Treatment-Seeking for Cocaine Dependence

Background: Cocaine-dependent individuals demonstrate attentional bias when measured by Stroop color-naming tasks that have been modified to include cocaine-related words. However, the relationship between attentional bias and the treatment-seeking status of cocaine-dependent individuals has never been explored. The purpose of this study was to compare attentional bias towards cocaine-related verbal stimuli between treatment-seeking and nontreatment-seeking cocaine abusers. Methods: We examined performance on a Stroop task modified to include drug-related words in 17 cocaine-dependent treatment-seeking male participants and 20 cocaine-dependent nontreatment-seeking male participants. Results: Although treatment seekers reported less experience with cocaine than nontreatment seekers, they exhibited increased response latency and made more errors when identifying the colors of cocaine-related words, relative to neutral words (p < .05), whereas nontreatment seekers did not. Conclusions: Factors other than a high frequency of cocaine use may contribute to the difference in attentional bias towards cocaine cues between these subgroups of cocaine users.

Priming with BTCP, a dopamine reuptake blocker, reinstates cocaine-seeking and enhances cocaine cue-induced reinstatement

N-[1-(2-benzo[ b]thiophenyl)cyclohexyl]piperidine (BTCP), a potent dopamine reuptake inhibitor, substitutes for the reinforcing effects of cocaine and meets other criteria for possible agonist pharmacotherapeutic potential. The purpose of this study was to determine (1) whether BTCP modifies reinstatement of cocaine-seeking elicited by cocaine-related environmental stimuli and (2) whether this compound produces priming effects. Male Wistar rats were trained to associate discriminative stimuli (S D) with cocaine availability (0.25 mg/infusion) versus non-reward and then were subjected to repeated extinction sessions during which the reinforcer and S D were withheld. Subsequent presentation of the cocaine S D produced recovery of cocaine-seeking. BTCP (2.5–30 mg/kg; i.p.) did not attenuate the conditioned reinstatement induced by the cocaine S D but, rather, potentiated this effect at 10 mg/kg. To test whether BTCP, by itself, exerts priming effects, different groups of rats were trained to self-administer cocaine (0.25 mg/infusion) for 2 weeks. After a 2-week extinction period, BTCP (5, 10 and 20 mg/kg, i.p.) reinstated cocaine-seeking, showing that BTCP not only increases cocaine-seeking induced by cocaine-related stimuli but also produces priming effects following abstinence. The results suggest that, in cocaine abstinent rats, BTCP produces cocaine-like effects.