RELAPSE TO HEROIN-SEEKING IN RATS UNDER OPIOID MAINTENANCE - THE EFFECTS OF STRESS, HEROIN PRIMING, AND WITHDRAWAL

It is widely believed that opioid withdrawal symptoms contribute to re lapse to opioid use, but relapse is highly probable in experienced use rs even after prolonged abstinence and during opioid maintenance thera py. We have found using an animal model of relapse, the reinstatement procedure, that the two events that reliably reinstate heroin-seeking behavior are reexposure to heroin, and brief exposure to footshock str ess. Contrary to expectation, opioid antagonist-induced withdrawal doe s not reinstate heroin-seeking. We now report on reinstatement of hero in-seeking in rats trained to self-administer heroin and subsequently exposed to a maintenance dose of heroin via minipump and allowed to se lf-administer saline. With the minipump in, naloxone-induced withdrawa l did not reinstate drug-seeking, a priming injection of heroin was on ly mildly effective, and footshock was highly effective. Twenty-four h ours after removal of the minipump (spontaneous withdrawal), animals r einitiated heroin-seeking and, subsequently, both heroin and footshock reinstated heroin-seeking. In summary, brief exposure to stress reins tated heroin-seeking in both heroin-maintained and withdrawn animals. The heroin prime reliably reinstated drug-seeking only in the absence of the minipump; opioid ''withdrawal,'' as such, did not reinstate dru g-seeking behavior. Naloxone given to heroin-maintained animals induce d withdrawal symptoms, caused a mild depression in the levels of dopam ine and its metabolites in the nucleus accumbens septi (NAS), but did not reinstate drug-seeking. Reinstatement of heroin-seeking during spo ntaneous withdrawal was not accompanied by reductions in basal dopamin e and its metabolites in NAS.