Kappa opioid inhibition of morphine and cocaine self-administration in rats

Kappa opioid inhibition of morphine and cocaine self-administration in rats Two kappa agonists, U50,488 and spiradoline, produced dose-related acute decreases in both morphine and cocaine self-administration in rats; higher doses of both agents were required to decrease rates of bar-pressing for water. On the day after kappa agonist administration, both agents produced extinction-like patterns of responding in many rats self-administering morphine or cocaine but not in rats responding for water. Two days after their administration, both U50,488 and spiradoline produced significant decreases in both morphine and cocaine intake; some rats continued to show decreases in drug self-administration for 5–6 days. Although the kappa antagonist nor-binaltorphimine (10 mg/kg s.c.) had no effect itself on either morphine or coccaine self-administration, it fully antagonized the effects of U50,488 (10 m/kg i.p.). The results suggest that although endogenous kappa opioid systems may not tonically modulate mechanisms involved in drug reinforcement, pharmacological activation of kappa pathways may be a novel and effective pharmacological approach to treating both opioid and stimulant addiction. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Kappa opioid inhibition of morphine and cocaine self-administration in rats

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Science B.V. All rights reserved
ISSN
0006-8993
DOI
10.1016/0006-8993(95)00306-B
Publisher site
See Article on Publisher Site

Abstract

Two kappa agonists, U50,488 and spiradoline, produced dose-related acute decreases in both morphine and cocaine self-administration in rats; higher doses of both agents were required to decrease rates of bar-pressing for water. On the day after kappa agonist administration, both agents produced extinction-like patterns of responding in many rats self-administering morphine or cocaine but not in rats responding for water. Two days after their administration, both U50,488 and spiradoline produced significant decreases in both morphine and cocaine intake; some rats continued to show decreases in drug self-administration for 5–6 days. Although the kappa antagonist nor-binaltorphimine (10 mg/kg s.c.) had no effect itself on either morphine or coccaine self-administration, it fully antagonized the effects of U50,488 (10 m/kg i.p.). The results suggest that although endogenous kappa opioid systems may not tonically modulate mechanisms involved in drug reinforcement, pharmacological activation of kappa pathways may be a novel and effective pharmacological approach to treating both opioid and stimulant addiction.

Journal

Brain ResearchElsevier

Published: May 29, 1995

References

  • The kappa-opioid U-50,488H suppresses the initiation of nocturnal spontaneous drinking in normally hydrated rats
    Badiani, A.; Stewart, J.
  • Changes in morphine self-administration after brainstem lesions in rats
    Glick, S.D.; Cox, R.D.
  • Food deprivation and stimulant self-administration in rats: differences between cocaine and d-amphetamine
    Glick, S.D.; Hinds, P.A.; Carlson, J.N.

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