Stress reinstates heroin-seeking in drug-free animals: An effect mimicking heroin,not withdrawal |
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Authors: | Y. Shaham J. Stewart |
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Affiliation: | (1) Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, 1455 de Maisonneuve Blvd., H3G 1M8 Montreal, Quebec, Canada |
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Abstract: | 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 µg/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. |
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Keywords: | Footshock Heroin Intravenous drug self-administration In vivo microdialysis Naltrexone Opioid drugs Relapse Reinstatement Stress Withdrawal |
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