Effects of naloxone on plasma corticosterone in the opiate-naive rat

Naloxone HCl (NX) has long been considered to be a pure narcotic antagonist, having an effect only subsequent to pretreatment with a narcotic. Characteristically, low doses of NX have been used to antagonize the effects of analgesic doses of narcotics and to precipitate withdrawal in chronically treated animals. In this study, the effects of high doses of NX (2.0–20.0 mg/kg) on changes in plasma corticosterone were examined in the opiate-naive animal. Using male rats with chronic intravenous catheters and one-way vision boxes, injections were made and serial blood samples were obtained in the conscious, unrestrained animal. The acute administration of NX to the opiate-naive animal produced a dose-related increase in plasma corticosterone with respect to both amplitude and duration. NX (10.0 mg/kg i.v.) produced a significant elevation in hormone level at 15 and 30 minutes. With NX (20.0 mg/kg i.v.) the duration of the response was extended to 60 minutes. To examine whether short-term tolerance to this effect could be produced, animals were given a single pretreatment with either NX (10.0 mg/kg) or saline i.v. Two hours later NX produced a similar elevation in hormone level in both groups. The effect of chronic injection of NX was also studied. Animals pretreated with either NX (10.0 mg/kg) or saline s.c. once daily for 7 days did not show a significant difference following the subsequent administration of NX. In both cases, a significant elevation of plasma corticosterone resulted. The results suggest that NX may have a direct effect on opiate receptors resulting in an elevation of plasma hormone levels or NX may be disrupting an endogenous opiate-receptor interaction producing a stress response.