Effect of chronic naltrexone and methadone administration on brain immunoreactive beta-endorphin in the rat.
The effects of chronic treatment with methadone, a long-acting opiate agonist, and naltrexone, a long-acting opiate antagonist on brain immunoreactive beta-endorphin (IR-beta-EP) concentrations were studied in the rat. Male rats were treated for 30 days with either methadone, 2.5 mg/kg/day; naltrexone 2 mg/kg/day, or saline. In a repeat experiment, rats were treated for 36 days with either methadone 2.5 mg/kg/day; naltrexone 4 mg/kg/day, or saline. Brain regions were homogenized in 0.2 N HCl and assayed for IR-beta-EP by RIA. No change in the IR-beta-EP content of the hypothalamus, thalamus, midbrain, or amygdala was measured in either experiment after methadone treatment. Naltrexone, however, significantly lowered brain IR-beta-EP in both experiments. In the first study hypothalamic IR-beta-EP fell from 189 +/- 17 (SEM) to 132 +/- 7.0 ng/g wet weight of tissue after naltrexone treatment (p less than 0.01). In the second experiment naltrexone lowered IR-beta-EP in the hypothalamus from 23.4 +/- 3.6 to 15.5 +/- 1.2 ng/mg protein (p less than 0.005). Similar decreases in the IR-beta-EP content of the thalamus (from 6.74 +/- 0.59 to 4.59 +/- 0.38 ng/mg protein) and amygdala (from 1.31 +/- 0.08 to 0.90 +/- 0.10) were also measured (p less than 0.01). We conclude that occupancy of opiate receptors by an opiate antagonist reduces brain levels of IR-beta-EP and suggests that chronic opiate receptor blockade may result in a compensatory increase in brain beta-EP release.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004723:Endorphins / Q000032:analysis*; D007031:Hypothalamus / Q000032:analysis; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009270:Naloxone / Q000031:analogs & derivatives*; D009271:Naltrexone / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D004723:Endorphins; D009270:Naloxone; D009271:Naltrexone; D001615:beta-Endorphin; D008691:Methadone