The contribution of drug history and time since termination of drug taking to footshock stress-induced cocaine seeking in rats

Rationale: There is reason to think that footshock stress-induced reinstatement of cocaine may be affected by the history of drug use and time since termination of drug taking. Objectives: Here, we assessed the contribution of daily access (hours per day) and duration (number of days) of cocaine self-administration to propensity to reinstate drug seeking following footshock stress at three time points following cocaine self-administration. Methods: Rats were trained to self-administer cocaine (0.5 mg kg(-1) infusion(-1)) on a fixed ratio 1 schedule in one of four training combinations of hours per day and number of days [2/7, 2/21, 12/7, and 12/21 (h/day)]. Rats were then tested for the first time under extinction conditions at either day 1, 10, or 60 after termination of cocaine availability. Once extinction criterion was met (<15 lever presses in 1 h), rats were then tested for stress-induced reinstatement after 15 min of intermittent, inescapable footshock (0.8 mA, 0.5 s/shock, mean off period of 40 s). Results: Rats that were given 12-h access to cocaine during training responded less in tests of extinction than those rats given 2-h access. Rats in all groups tested in extinction at days 10 and 60 showed higher responding than at day 1, suggesting an incubation of responding. In footshock stress-induced reinstatement tests, rats with greater exposure to cocaine showed a similar suppression of responding at day 1 and enhanced responding at day 60. As expected, rats that were given 12-h/21-day access to cocaine had the greatest intake of cocaine across the training phase with a slow escalation of hourly intake. Conclusion: Greater access to cocaine results in suppression of cocaine seeking following footshock stress at early time points and a progressive increase over time.