Naltrexone induces melanocyte-stimulating hormone release and degenerative changes in pituitary innervation in...

Adult Rana pipiens (common frog) were treated with the long-acting opiate antagonist drug naltrexone hydrochloride to study potential effects of an opiate-receptor block on release of pro-opiomelanocortin (POMC) peptides from the pituitary intermediate lobe. The melanophore response of the animals was used to assess relative release of melanocyte-stimulating hormone (MSH). Animals were adapted to a light background, then injected with 20 or 50 mg/kg naltrexone for up to 3.5 days. All drug-treated animals showed increased release of MSH while on the light background while controls remained light-adapted. Ultrastructure of the pars intermedia of naltrexone-treated frogs revealed nerve fibers containing myelin figures, swelling of neurovesicles, and abnormal membrane components indicative of degenerative changes. The observations suggest that naltrexone has a damaging effect on pituitary innervation, and that MSH release may be the result of loss of neuroregulation from the normally inhibitory innervation. The findings are in agreement with our earlier studies in rats, which also demonstrated degenerative changes induced by naltrexone in intermediate lobe innervation. The long-acting antagonist may therefore have a "neurotoxic" effect after multiple injections or chronic use.