Abstract
Cocaine use disorder is characterized not only by the high rate of relapse, but also by deficits in cognition and prefrontal cortical function. Still, the relationship between cognitive impairment and cocaine-seeking remains poorly understood. The current study used a rodent model to determine the effects of extended access cocaine self-administration on cognitive performance in a prefrontal cortex-dependent delayed match-to-sample/non-match-to-sample (DMS/DNMS) task. Further, this study sought to investigate how post-cocaine changes in cognitive performance correlate with cue/context-induced cocaine-seeking following a prolonged period of abstinence. Animals were trained to self-administer cocaine during 6 daily 1 hour-long sessions followed by 12 days of extended, 6 hour-long access. The extended access cocaine rats exhibited robust self-administration behavior and escalation of cocaine intake. Next, DMS/DNMS task was used to evaluate working memory capacity and reversal learning performance over a range of 0 - 30 s delays. Although this study failed to detect a major cognitive impairment, extended access to cocaine resulted in the persistent working memory/DMS deficit at a moderate cognitive load (10 s delay). There were no changes in the reversal learning/DNMS performance. It is likely that the parameters of the DMS/DNMS task, as used in the current study, exceeded acquisition capacity of rats thus obscuring cocaine effects at longer delays. Finally, rats showed a robust relapse of context/cue-elicited cocaine-seeking following the 45 - day abstinence. However, the intensity of cocaine-seeking did not correlate with the deficit in the DMS task. In conclusion, future studies must re-evaluate whether a more robust relationship between post-cocaine cognitive performance and cocaine-seeking can be detected under adjusted DMS/DNMS conditions.
Highlights
Cocaine addiction is a chronic relapsing disorder, characterized by compulsive drug seeking and decreased ability to limit intake [1]
This study sought to examine the effect of extended access cocaine self-administration on working memory performance and reversal learning capacity, and to further explore the relationship between these post-cocaine cognitive deficits and drug-seeking during a 45 day period of cocaine abstinence
This study utilized a novel combination of (1) drug self-administration with (2) an operant delayed match-to-sample (DMS)/DNMS task and (3)-induced relapse that allowed for the sequential assessment of behavioral parameters in the same group of animals
Summary
Cocaine addiction (cocaine use disorder) is a chronic relapsing disorder, characterized by compulsive drug seeking and decreased ability to limit intake [1]. In support, decreased activity of the PFC ( termed hypofrontality) has been documented in subjects with cocaine use disorder using functional imaging [3]. Coinciding with hypofrontality is the emergence of cognitive impairments mainly related to attention, working memory, impulsivity and cognitive flexibility [4-. We evaluated the performance in a PFC-dependent, operant delayed match-to-sample (DMS) / non match-to-sample (DNMS) task (see [17]) in animals with a history of extended cocaine self-administration. To investigate the link between PFC-dependent cognitive dysfunction and drug-seeking, animals underwent (cue + context)-induced reinstatement, following the completion of the DMS/DNMS testing. We hypothesized that a history of extended access to cocaine would decrease working memory performance, impede reversal learning and that these cognitive impairments would correlate with increased (incubated) cocaine-seeking after protracted, 45 day-long abstinence
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