Effect of antagonists selective for mu, delta and kappa opioid receptors on the reinforcing effects of heroin in rats.
Antagonists selective for mu, delta and kappa-opioid receptors were evaluated for their effects on responding maintained by i.v. injections of heroin (60.0 micrograms/kg/injection) in rats during daily 3-hr sessions. Under base-line conditions, rats self-administered 10 to 20 heroin injections during each session, and injections were separated by relatively constant interinjection intervals of about 10 to 20 min. The mu-selective antagonist beta-funaltrexamine (beta-FNA; 5.0-20.0 mg/kg, s.c.) produced a dose-dependent increase in responding for heroin, with some doses of beta-FNA producing an extinction-like pattern of responding. These results were qualitatively similar to the effect obtained by lowering the unit dose per injection of heroin. The mu 1-selective antagonist naloxonazine (NXZ; 7.5-30.0 mg/kg, i.v.) and the delta-selective antagonist naltrindole (1.0-17.0 mg/kg) also produced dose-dependent increases in heroin self-administration, but neither naloxonazine nor naltrindole produced extinction-like patterns of responding. The kappa-selective antagonist nor-binaltorphimine (nor-BNI; 5.0-10.0 mg/kg, s.c.) had no effect on heroin self-administration. These results indicate that mu receptors play an important role in mediating the reinforcing effects of heroin in the rat. Delta and mu 1 receptors, but not kappa receptors, may also be involved.
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
S S
SS
Negus
S J
SJ
Henriksen
A
A
Mattox
G W
GW
Pasternak
P S
PS
Portoghese
A E
AE
Takemori
M B
MB
Weinger
G F
GF
Koob
D000818:Animals; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D012646:Self Administration
D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D003932:Heroin; C024524:beta-funaltrexamine; C034643:naloxonazine; C055382:naltrindole