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 off period of 40 s) reinstated heroin-seeking behavior in heroin-experienced, drug-free rats after many sessions of extinction and up to 6 weeks after last exposure to heroin. In reinstating the behavior, the footshock mimicked the effect of a non-contingent priming infusion of heroin (50 micrograms/kg). By contrast, the aversive state of acute opioid withdrawal induced by injection of the opioid receptor antagonist naltrexone (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 region of the mesolimbic dopamine system implicated in the reinforcing effects of drugs. Similarly, dopamine overflow was increased by an injection of 10 mg/kg morphine, SC, an effect that was reversed by an injection of 5 mg/kg naltrexone given 40 min after to induce the withdrawal condition. A possible interpretation of the present results is that stressors can reinstate drug-taking behavior by activating neural systems in common with those activated by heroin.
Shaham
Y
Y
Department of Psychology, Concordia University, Montreal, Quebec, Canada.
Stewart
J
J
D000818:Animals; D001522:Behavior, Animal; D004597:Electroshock; D005260:Female; D005528:Foot; D003932:Heroin / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological; D013997:Time Factors
D003932:Heroin; D009020:Morphine