Effects of opiate antagonists and their quaternary analogues on nucleus accumbens self-stimulation.
Naloxone and naltrexone were compared with their quaternary analogues naloxone methobromide and naltrexone methobromide for efficacy in suppressing intracranial self-stimulation behavior. These quaternary analogues effectively block opiate receptors in the periphery, but since they do not readily cross the blood-brain barrier they have little effect on central receptors. Rats with electrodes in the nucleus accumbens were trained to self-stimulate in daily 60-min sessions. Naloxone (0.2, 2.0 and 20 mg/kg) and naltrexone (20 mg/kg) potently suppressed self-stimulation behavior. In contrast, neither naloxone methobromide (0.2 and 20 mg/kg) nor naltrexone methobromide (20mg/kg) had any significant effects on this behavior. These results suggest that blockade of peripheral opiate receptors alone is insufficient to suppress self-stimulation, and therefore support the idea that opiate antagonists suppress self-stimulation by blockade of central receptors that mediate reinforcement.
Trujillo
K A
KA
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
Belluzzi
J D
JD
Stein
L
L
D000818:Animals; D001931:Brain Mapping; D008297:Male; D009042:Motivation / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D010111:Oxymorphone / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D012653:Self Stimulation / Q000187:drug effects*; D012686:Septal Nuclei / Q000187:drug effects*
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D011957:Receptors, Opioid; C032257:methylnaltrexone; D009270:Naloxone; D009271:Naltrexone; D010111:Oxymorphone