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 exti...

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Bibliographic Details
Published in:Brain research 1995-05, Vol.681 (1), p.147-152
Main Authors: Glick, Stanley D., Maisonneuve, Isabelle M., Raucci, John, Sydney, Archer
Format: Article
Language:English
Subjects:
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Analgesics - pharmacology
Animals
Biological and medical sciences
Cocaine
Cocaine - administration & dosage
Cocaine - pharmacology
Dose-Response Relationship, Drug
Drug addictions
Drug self-administration
Extinction, Psychological - drug effects
Female
Kappa opioid
Medical sciences
Morphine
Morphine - administration & dosage
Morphine - pharmacology
Naltrexone - analogs & derivatives
Naltrexone - pharmacology
Narcotics - administration & dosage
Narcotics - pharmacology
Nor-binaltorphimine
Pyrrolidines - antagonists & inhibitors
Pyrrolidines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Opioid, kappa - agonists
Reinforcement (Psychology)
Self Administration
Spiradoline
Toxicology
U50,488
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Summary: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.
ISSN:0006-8993
1872-6240
DOI:10.1016/0006-8993(95)00306-B