IMPAIRED SUPERSENSITIVITY TO MORPHINE FOLLOWING CHRONIC NALTREXONE TREATMENT IN SENESCENT RATS

Chronic administration of opiate antagonists produces an increase in t he density of opiate receptors, as well as an enhanced sensitivity to the analgesic and locomotor depressant effects of morphine. The presen t study assessed whether aging alters these regulatory processes. Youn g (3-4 months), middle-aged (10-11 months), and senescent (25-30 month s) rats were implanted subdermally with slow-release naltrexone pellet s or were given sham surgery. The pellets were removed 10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg, SC) analgesia and locomotor activity were assessed. Young and middle-aged rats treated with naltrexone showed enhanced sensitivity to the analg esic and locomotor activity depressant effects of morphine relative to age-matched controls. In contrast, senescent rats treated with naltre xone did not differ from age-matched controls in their response to mor phine. The density of opiate receptors labeled with H-3-naloxone was m easured in the anterior striatum. Both young and senescent rats treate d with naltrexone exhibited an increase in opiate receptor density rel ative to age-matched controls. The results indicate that senescent rat s are capable of up-regulating opiate receptors following chronic nalt rexone treatment but do not exhibit the corresponding functional super sensitivity to morphine.