Cocaine seeking over extended withdrawal periods in rats: time dependent increases of responding induced by heroin priming over the first 3 months.

RATIONALE: Using a rat relapse model, recent studies reported time dependent increases in cocaine seeking induced by re-exposure to cocaine cues, but not cocaine itself, over withdrawal periods of up to 3 months.
OBJECTIVES: In the present study, we explored the time course of cocaine seeking induced by priming injections of heroin over the first 3 months of withdrawal from cocaine.
METHODS: Rats were trained to self-administer intravenous cocaine for 6 h/day over a period of 10 days. Cocaine seeking induced by heroin priming was then assessed in different groups of rats after 1 day, and 1 and 3 months of withdrawal from cocaine. During the test day, rats were first given six 1-h extinction sessions. Subsequently, reinstatement of cocaine seeking induced by non-contingent saline and heroin injections (0.125 and 0.25 mg/kg, s.c.) was assessed during three 1-h sessions.
RESULTS: As in previous studies, extinction responding was substantially greater after 1 and 3 months of withdrawal than after 1 day. More importantly, we also found that the effect of heroin priming on reinstatement of cocaine seeking is time dependent, with higher responding occurring after 1 and 3 months than after 1 day.
CONCLUSION: The present results replicate previous findings on the time dependent increases in resistance to extinction after withdrawal from cocaine, and further indicate that the duration of the drug withdrawal period is a critical modulator of the effect of heroin priming on cocaine seeking. These data may have implications for the treatment of cocaine relapse induced by other drugs.