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Potentiation of brain stimulation reward by morphine: effects of neurokinin-1 receptor antagonism

Authors
  • Robinson, J. E.1
  • Fish, E. W.1
  • Krouse, M. C.1
  • Thorsell, A.2
  • Heilig, M.2
  • Malanga, C. J.1
  • 1 University of North Carolina at Chapel Hill, Department of Neurology and Bowles Center for Alcohol Studies, 170 Manning Dr., CB 7025, Chapel Hill, NC, 27599-7025, USA , Chapel Hill (United States)
  • 2 National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Laboratory of Clinical and Translational Studies, Bethesda, MD, USA , Bethesda (United States)
Type
Published Article
Journal
Psychopharmacology
Publication Date
Sep 10, 2011
Volume
220
Issue
1
Pages
215–224
Identifiers
DOI: 10.1007/s00213-011-2469-z
Source
Springer Nature
Keywords
License
Yellow

Abstract

RationaleThe abuse potential of opioids may be due to their reinforcing and rewarding effects, which may be attenuated by neurokinin-1 receptor (NK1R) antagonists.ObjectiveThis study was conducted to measure the effects of opioid and NK1R blockade on the potentiation of brain stimulation reward (BSR) by morphine using the intracranial self-stimulation method.MethodsAdult male C57BL/6J mice (n = 15) were implanted with unipolar stimulating electrodes in the lateral hypothalamus and trained to respond for varying frequencies of rewarding electrical stimulation. The BSR threshold (θ0) and maximum response rate (MAX) were determined before and after intraperitoneal administration of saline, morphine (1.0–17.0 mg/kg), or the NK1R antagonists L-733,060 (1.0–17.0 mg/kg) and L-703,606 (1.0–17.0 mg/kg). In morphine antagonism experiments, naltrexone (0.1–1.0 mg/kg) or 10.0 mg/kg L-733,060 or L-703,606 was administered 15 min before morphine (1.0–10.0 mg/kg) or saline.ResultsMorphine dose-dependently decreased θ0 (maximum effect = 62% of baseline) and altered MAX when compared to saline. L-703,606 and L-733,060 altered θ0; 10.0 mg/kg L-733,060 and L-703,606, which did not affect θ0 or MAX, attenuated the effects of 3.0 and 10.0 mg/kg morphine, and 1.0 and 0.3 mg/kg naltrexone blocked the effects of 10.0 mg/kg morphine. Naltrexone given before saline did not affect θ0 or MAX.ConclusionsThe decrease in θ0 by morphine reflects its rewarding effects, which were attenuated by NK1R and opioid receptor blockade. These results demonstrate the importance of substance P signaling during limbic reward system activation by opioids.

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