STRESS REINSTATES HEROIN-SEEKING IN DRUG-FREE ANIMALS - AN EFFECT MIMICKING HEROIN, NOT WITHDRAWAL

Exposure to 10 min of footshock stress (1 mA; 0.5 s on, with a mean of f period of 40 s) reinstated heroin-seeking behavior in heroin-experie nced, drug-free rats after many sessions of extinction and up to 6 wee ks after last exposure to heroin. In reinstating the behavior, the foo tshock mimicked the effect of a non-contingent priming infusion of her oin (50 mu g/kg). By contrast, the aversive state of acute opioid with drawal induced by injection of the opioid receptor antagonist naltrexo ne (5 mg/kg, SC), following an acute injection of morphine (10 mg/kg, SC), had no effect on heroin-seeking behavior. In a second experiment it was shown in drug naive animals that these parameters of footshock increased dopamine overflow in the nucleus accumbens, a terminal regio n of the mesolimbic dopamine system implicated in the reinforcing effe cts of drugs. Similarly, dopamine overflow was increased by an injecti on of 10 mg/kg morphine, SC, an effect that was reversed by an injecti on of 5 mg/kg naltrexone given 40 min after to induce the withdrawal c ondition. A possible interpretation of the present results is that str essors can reinstate drug-taking behavior by activating neural systems in common with those activated by heroin.