Effects of opiate antagonists and their quaternary derivatives on heroin self-administration in the rat
Koob, G.F.; Pettit, H.O.; Ettenberg, A.; Bloom, F.E.
Journal of Pharmacology and Experimental Therapeutics 229(2): 481-486
1984
ISSN/ISBN: 0022-3565 PMID: 6716270 Document Number: 237470
Quaternary derivatives of naloxone and naltrexone, methyl naloxonium chloride (ORG 10908) and naltrexone methobromide (MRZ 2663BR), respectively, were compared with the parent compounds for their ability to antagonize the reinforcing properties of heroin as measured in an operant, i.v., self-administration paradigm. As expected, lower doses (up to 0.2 mg/kg) of naloxone and naltrexone produced dose-dependent increases in heroin self-administration, but at higher doses (10-30 mg/kg) these drugs produced transient decreases (20-100 min) in self-administrtion followed by recovery. Naltrexone was approximately 1.5 times more potent than naloxone in increasing heroin self-administration at the lower doses (up to 0.2 mg/kg) and had a slightly longer duration of action. The quaternary derivatives were ineffective as antagonists of heroin self-administration in doses 200 times greater than the effective antagonist dose of naloxone or naltrexone. Evidently the acute reinforcing properties of i.v. opiates associated with the sensation of the rush involve opiate receptors located within the CNS and do not involve peripheral opiate receptors.