Effect of prolyl-leucyl-glycinamide and alpha-melanocyte-stimulating hormone on levorphanol-induced analgesia, tolerance and dependence.
Prolyl-leucyl-glycinamide (PLG) at a low dose (10 ng/mouse) administered by an intracerebroventricular (i.c.v.) injection did not affect levorphanol analgesia, but PLG at higher doses (10 and 100 micrograms/mouse) and alpha-melanocyte-stimulating hormone (alpha-MSH) (10 ng/mouse) antagonized levorphanol analgesia. Development of levorphanol tolerance was facilitated by 10 ng/mouse of PLG, unaffected by 10 micrograms/mouse of PLG, but antagonized by 100 micrograms/mouse of PLG and 10 ng/mouse of alpha-MSH. The effect of PLG on levorphanol dependence was assessed by changes in body weight and temperature during naloxone-induced withdrawal. PLG (10 ng/mouse) facilitated the development of levorphanol dependence, but 10 micrograms/mouse of PLG had no effect. PLG (100 micrograms/mouse) antagonized development of levorphanol dependence. PLG at doses of 10 and 100 micrograms/mouse precipitated withdrawal in levorphanol-dependent mice. alpha-MSH (10 ng/mouse) antagonized development of levorphanol dependence as evidenced by an increase in the ED50 of naloxone required to induce withdrawal jumping. These results indicate that PLG and alpha-MSH affected levorphanol-induced analgesia, tolerance and dependence in a qualitatively similar manner to their effect on morphine-induced analgesia, tolerance and dependence.
D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006801:Humans; D007981:Levorphanol / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D051379:Mice; D009270:Naloxone; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced; D019966:Substance-Related Disorders
D007981:Levorphanol; D009270:Naloxone; D009074:Melanocyte-Stimulating Hormones; D009075:MSH Release-Inhibiting Hormone