MORPHINE-INDUCED SUPER-SENSITIVITY TO THE EFFECTS OF NALOXONE ON LUTEINIZING-HORMONE SECRETION IN THE MALE-RAT

Google Scholar
  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (1) , 35-41
Abstract
The effects of morphine pretreatment on naloxone-induced increases in serum luteinizing hormone (LH) levels were examined in male rats. After a single morphine injection (10 mg/kg), naloxone (0.5 mg/kg)-induced increases in serum LH levels were initially suppressed (0-3 h), but returned to normal by 4 h. Five to 24 h after morphine pretreatment naloxone-precipitated increases in LH were markedly exaggerated with the peak effect occuring at 6 h (4 times greater than saline-pretreated controls). In morphine-implanted rats (75-mg pellet, 48 h earlier), the enhanced sensitivty to naloxone was considerably more dramatic than that found after acute administration. Naloxone-induced increases in serum LH levels were > 40 to 50 times greater in serum-implanted animals than they were in placebo-implanted rats at the respective ED50 dose. Naloxone dose-response curves revealed that the naloxone ED50 was reduced by either morphine pretreatment regimen, but was much more pronounced in pellet-impanted animals [181.6 .mu.g/kg in controls; 116.4 .mu.g/kg in acutely morphinized animals (P < 0.05); and 4.39 .mu.g/kg in morphine-impanted rats (P < 0.001)]. The only distinction between acute and chronic morphine administration was in the magnitude of the shift in the naloxone ED50 as identical peak increases in LH were obtained in both groups. Apparently, naloxone-induced increases in serum LH levels can serve as a useful and sensitive means to assess opiate dependence. The mechanisms underlying the morphine-induced enhancement of the effects of naloxone on serum LH levels are not fully understood, but no differences in the uptake of naloxone into brain as a function of morphine pretreatment were found.