Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats.
نویسندگان
چکیده
Drug addicts make poor decisions. These decision-making deficits have been modeled in addicts and laboratory animals using reversal-learning tasks. However, persistent reversal-learning impairments have been shown in rats and monkeys only after noncontingent cocaine injections. Current thinking holds that to represent the human condition effectively, animal models of addiction must utilize self-administration procedures in which drug is earned contingently; thus, it remains unclear whether reversal-learning deficits caused by noncontingent cocaine exposure are relevant to addiction. To test whether reversal learning deficits are caused by contingent cocaine exposure, we trained rats to self-administer cocaine, assessed cue-induced cocaine seeking in extinction tests after 1 and 30 d of withdrawal, and then tested for reversal learning more than a month later. We found robust time-dependent increases in cue-induced cocaine seeking in the two extinction tests (incubation of craving) and severe reversal-learning impairments.
منابع مشابه
A switch in the neuromodulatory effects of dopamine in the oval bed nucleus of the stria terminalis associated with cocaine self-administration in rats.
Chronic exposure to drugs of abuse alters brain reward circuits and produces functional changes in the dopamine (DA) system. However, it is not known whether these changes are directly related to drug-driven behaviors or whether they simply are adaptive responses to long-term drug exposure. Here, we combined the rat model of cocaine self-administration with brain slice electrophysiology to iden...
متن کاملIncreased impulsivity during withdrawal from cocaine self-administration: role for DeltaFosB in the orbitofrontal cortex.
Increased impulsivity caused by addictive drugs is believed to contribute to the maintenance of addiction and has been linked to hypofunction within the orbitofrontal cortex (OFC). Recent data indicate that cocaine "self-administration" induces the transcription factor DeltaFosB in the OFC that alters the effects of investigator-administered cocaine on impulsivity. Here, using viral-mediated ge...
متن کاملDeficits in ventromedial prefrontal cortex group 1 metabotropic glutamate receptor function mediate resistance to extinction during protracted withdrawal from an extensive history of cocaine self-administration.
Anomalies in prefrontal cortex (PFC) function are posited to underpin difficulties in learning to suppress drug-seeking behavior during abstinence. Because group 1 metabotropic glutamate receptors (mGluRs) regulate drug-related learning, we assayed the consequences of extended access to intravenous cocaine (6 h/d; 0.25 mg/infusion for 10 d) on the PFC expression of group 1 mGluRs and the releva...
متن کاملThe Effects of Extended-Access Cocaine Self-Administration on Working Memory Performance, Reversal Learning and Incubation of Cocaine-Seeking in Adult Male Rats
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 co...
متن کاملChronic cocaine self-administration in rhesus monkeys: impact on associative learning, cognitive control, and working memory.
Cocaine users display a wide range of cognitive impairments. Because treatment outcome is dependent on baseline cognitive ability, it is clinically important to understand the underlying neurobiology of these deficits. Therefore, it is crucial to determine whether cocaine exposure by itself is an etiological factor and, if so, to determine the overall nature of cognitive deficits associated wit...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Learning & memory
دوره 14 5 شماره
صفحات -
تاریخ انتشار 2007