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

• Published in: Brain research Vol. 681; no. 1; pp. 147 - 152
• Main Authors: Glick, Stanley D., Maisonneuve, Isabelle M., Raucci, John, Sydney, Archer
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 29-05-1995; Amsterdam Elsevier; New York, NY
• 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; Drug self-administration; U50,488; Kappa opioid; Spiradoline; Morphine; Cocaine; Nor-binaltorphimine; Vertebrata; Mammalia; Rat; Animal; Rodentia; Reinforcement; Drug of abuse; Self administration; Opiate receptor κ
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00306-B

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.