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 cocaine 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.
Glick
S D
SD
Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208, USA.
Maisonneuve
I M
IM
Raucci
J
J
Archer
S
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012054:Reinforcement, Psychology; D012646:Self Administration
D000700:Analgesics; D009294:Narcotics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D003042:Cocaine; C051272:spiradoline