Effect of Chronic Naltrexone and Methadone Administration on Brain Immunoreactive β-Endorphin in the Rat

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Abstract
The effects of chronic treatment with methadone, a long-acting opiate agonist, and naltrexone, a long-acting opiate antagonist on brain immunoreactive β-endorphin (IR-β-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 iVHCl and assayed for IR-β-EPby RIA. No change in the IR-β-EP content of the hypothalamus, thalamus, midbrain, or amygdala was measured in either experiment after methadone treatment. Naltrexone, however, significantly lowered brain IR-β-EP in both experiments. In the first study hypothalamic IR-β-EP fell from 189 ± 17 (SEM) to 132 ± 7.0 ng/g wet weight of tissue after naltrexone treatment (p < 0.01). In the second experiment naltrexone lowered IR-β-EP in the hypothalamus from 23.4 ± 3.6 to 15.5 ± 1.2 ng/mg protein (p < 0.005). Similar decreases in the IR-β-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 < 0.01). We conclude that occupancy of opiate receptors by an opiate antagonist reduces brain levels of IR-β-EP and suggests that chronic opiate receptor blockade may result in a compensatory increase in brain β-EP release.