Modulation of morphine-induced sensitization by endogenous kappa opioid systems in the rat.
Sensitization to both the motor stimulant and mesolimbic dopamine-releasing effects of morphine were studied in animals chronically treated with morphine and those that had received the kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI) prior to the commencement of morphine treatment. Rats were pretreated with either nor-BNI (30 micrograms; i.c.v.) or its vehicle and then received injections of morphine for 10 days. Locomotor activity and microdialysis studies were then conducted 3 and 30 days after termination of the chronic morphine treatment. In chronic morphine-treated rats, sensitization developed to both the motor stimulatory effects of morphine and the mesolimbic dopamine-releasing effects of this drug. Sensitization was observed 3 and 30 days after termination of morphine treatment. In animals pretreated with nor-BNI, sensitization to both the motoric and dopamine-releasing effects of morphine was significantly greater than that of chronic morphine-treated rats. These results suggest that endogenous kappa opioid systems play an important role in morphine-induced sensitization and that manipulations of these systems can markedly influence both its behavioral and neurochemical expression.
Department of Neuroendocrinology, Max-Planck-Institute of Psychiatry, Clinical Institute, Munich, FRG.
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Spanagel
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Shippenberg
D000818:Animals; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D007276:Injections, Intraventricular; D008032:Limbic System / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects*
D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; D004298:Dopamine