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Endogenous κ-opioid systems in opiate withdrawal: role in aversion and accompanying changes in mesolimbic dopamine release

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Abstract

The κ-opioid receptor antagonist nor-binaltor-phimine (nor-BNI) was recently shown to potentiate certain overt withdrawal signs in morphine-dependent rats. The present study sought to further assess this phenomenon by examining the influence of nor-BNI treatment upon the conditioned place aversion associated with the naloxone-precipitated withdrawal syndrome. In addition, in vivo microdialysis studies were conducted in morphine-dependent rats to determine whether nor-BNI treatment can modify withdrawal-induced changes in basal dopamine (DA) release within the mesolimbic system. Rats were pretreated with either saline or a single dose of nor-BNI and then received ascending doses of morphine for 10 days. A withdrawal syndrome was then precipitated by the administration of naloxone (1 mg/kg SC). In rats which received chronic morphine injections, administration of naloxone produced a characteristic withdrawal syndrome and a marked aversion for an environment previously associated with naloxone-precipitated withdrawal. Nor-BNI treatment potentiated most overt signs of physical dependence. This treatment also resulted in a greater withdrawal-induced place aversion. Morphine-dependent rats exhibited a marked reduction in basal mesolimbic DA release. An even greater decrease in basal DA release was observed in nor-BNI treated rats. These results suggest that endogenous κ-systems are important in the modulation of mesolimbic DA release and the accompanying place aversion which occurs during opiate withdrawal.

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Authors and Affiliations

  1. Department of Neuroendocrinology, Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, D-80804, Munich, Germany

    Rainer Spanagel, Osborne F. X. Almeida, Christine Bartl & Toni S. Shippenberg

  2. Department of Neuropharmacology, Max-Planck-Institute of Psychiatry, D-82152, Martinsried, Germany

    Rainer Spanagel

  3. Behavioral Pharmacology and Genetics Section, Preclinical Pharmacology Laboratory, Addiction Research Center, NIDA, Baltimore, MD, USA

    Toni S. Shippenberg

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  1. Rainer Spanagel
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  2. Osborne F. X. Almeida
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  3. Christine Bartl
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  4. Toni S. Shippenberg
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Spanagel, R., Almeida, O.F.X., Bartl, C. et al. Endogenous κ-opioid systems in opiate withdrawal: role in aversion and accompanying changes in mesolimbic dopamine release. Psychopharmacology 115, 121–127 (1994). https://doi.org/10.1007/BF02244761

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  • DOI: https://doi.org/10.1007/BF02244761

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