Impaired decision making following escalation of cocaine self-administration predicts vulnerability to relapse in rats.

Impairments in cost-benefit decision making represent a cardinal feature of drug addiction. However, whether these alterations predate drug exposure, thereby contributing to facilitating loss of control over drug intake, or alternatively arise as a result of drug use and subsequently confer vulnerability to relapse has yet to be determined. Male Sprague-Dawley rats were trained to self-administer (SA) cocaine during 19 daily long-access (12-h) sessions; conditions reliably shown to promote escalation. One week after cocaine SA, rats underwent an extinction/relapse test immediately followed by conditioned stimuli-, stress-, and drug-primed reinstatement challenges. The influence of escalated cocaine intake on decision making was measured over time by four test sessions of a rodent analogue of the Iowa Gambling Task (rGT), once prior to cocaine exposure and then 1 day, 1 week, and 1 month after the last SA session. Substantial individual variability was observed in the influence of escalated cocaine SA on decision-making performance. A subset of rats displayed pronounced deficits, while others showed unaffected or even improved performance on the rat Gambling Task (rGT) 24 hours after the last SA session. When challenged with a relapse test after 1 week of forced abstinence, animals that showed impaired decision making following SA displayed an increased propensity to respond for cocaine under extinction. These data suggest that decision-making deficits in individuals with drug addiction are not antecedent to-but arise as a consequence of-drug exposure. Moreover, these data indicate that susceptibility to the deleterious effects of drugs on decision making confers vulnerability toward relapse.

Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula.

RATIONALE: Increasing evidence suggests that the anterior insular cortex (AIC) plays a major role in cocaine addiction, being implicated in both impaired insight and associated decision-making and also craving and relapse. However, the nature of the involvement of the insula in the development and maintenance of cocaine addiction remains unknown, thereby limiting our understanding of its causal role in addiction. We therefore investigated whether pre- and post-training bilateral lesions of the AIC differentially influenced the development and the expression of the escalation of cocaine self-administration during extended access to the drug. METHODS: In a series of experiments, Sprague Dawley rats received bilateral excitotoxic lesions of the AIC either prior to, or after 3 weeks of training under 12-h extended self-administration conditions, which are known to promote a robust escalation of intake. We also investigated the influence of AIC lesions on anxiety, as measured in an elevated plus maze and sensitivity to conditioned stimuli (CS)- or drug-induced reinstatement of an extinguished instrumental response. RESULTS: Whereas, post-escalation lesions of the AIC, as anticipated, restored control over cocaine intake and prevented drug-induced reinstatement, pre-training lesions resulted in a facilitation of the development of loss of control with no influence over the acquisition of cocaine self-administration or anxiety. CONCLUSIONS: AIC lesions differentially affect the development and maintenance of the loss of control over cocaine intake, suggesting that the nature of the contribution of cocaine-associated interoceptive mechanisms changes over the course of escalation and may represent an important component of addiction.

The relationship between insight and uncertainty in obsessive-compulsive disorder.

BACKGROUND: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD). SAMPLING AND METHODS: Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the 'uncertainty cost' during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS). RESULTS: Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49). CONCLUSIONS: The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients. STUDY LIMITATIONS: The absence of a comparison group and the low number of included patients are the main limitations of the present study.