Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self-administration

摘要: Cocaine dependence is associated with orbitofrontal cortex (OFC)-dependent cognitive inflexibility in both humans and laboratory animals. A critical question whether cocaine self-administration affects pre-existing individual differences flexibility. Serotonin transporter knockout (5-HTT/) mice show improved flexibility a visual reversal learning task, whereas 5-HTT/ rats self-administer increased amounts of cocaine. Here we assessed: (1) also (next to mice); (2) this affected by self-administration, which these Results confirmed that naive (n=8) exhibit flexibility, as measured sucrose reinforced task. separate group was subsequently trained intravenously (0.5mg/kg/infusion), observed the (n=10) self-administered twice much [632.7mg/kg (+/- 26.3)] compared 5-HTT+/+ (n=6) [352.3mg/kg 62.0)] over 50 1-hour sessions. Five weeks into withdrawal cocaine-exposed animals were tested sucrose-reinforced paradigm. Interestingly, like rats, exposed displayed In conclusion, reflects trait preserved during cocaine-withdrawal. As rodents model low activity s-allele human serotonin transporter-linked polymorphic region, findings may have heuristic value treatment addicts.