Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats

摘要: Rationale and objectives: Footshock stress reliably reinstates heroin seeking in rats, but the time course of development this effect following drug withdrawal is not known. Here we studied intermittent footshock on reinstatement different periods (1–66 days). We also whether changes corticotropin-releasing factor (CRF) mRNA central nucleus amygdala (CeA) bed stria terminalis (BNST) are correlated with after 1 day 6 days withdrawal. Methods: Rats were trained to self-administer (9 h/day; 0.1 mg/kg per infusion) for 10 days. Tests extinction behavior footshock-induced then conducted 1, 6, 12, 25, or 66 days On test day, rats given five ten 60-min sessions until they reached criterion less than 15 responses 60 min lever previously associated heroin. exposed (0.8 mA; 10 min), lever-pressing was recorded 120 min. Results: Reinstatement by followed an inverted U-shaped curve maximal responding 12 days Surprisingly, did reinstate day 1 Lever pressing during extinction, prior exposure footshock, curve, higher 25 days Finally, compared control groups shock, CRF levels response increased CeA (day 1 withdrawal) dorsal BNST day 6), ventral BNST. Conclusions: The duration period important manifestation (1) stress-induced (2) heroin-reinforced behavior. time-dependent from alterations