The Anti-morphine-physical-dependence Effect Of Melatonin And Its Relation To β-endorphin In CNS

Melatonin has been known as a neuroendohormone synthesized and secreted primarily by the pineal gland, which can be synthesized chemically at present. Melatonin possesses some important physiological and pharmacological effects, and has very low toxicity. Therefore, the study on function of melatonin has been one of the most interesting research fields.The anti-drug-dependence effect of melatonin has been noted. Some study suggests that its action may be relative to the endoapeptides of CNS, but it needs to be further elucidated. Hence, in the present study, the effect of melatonin on drug-dependence was determined by GPI and mice of morphine-dependence. In order to make clear further the anti-drug-dependence effect of melatonin, we primarily study whether the effect is relative to theβ-endorphin of Arc and PAG in CNS.Result: (1) Isolated guinea-pig ileums were incubated with MLT(800μmol/l for 3h) can not produce withdrawl contractions. (2) Mouse which were intraperitoneal injection (ip) with MLT(40mg/kg) for 8 days can not produce withdrawl jumping and weight loss significantly. (3) MLT(25,100,400μmol/l, incubated with the morphine for 3 hours)significantly inhibited the contraction of morphine-dependent isolated guinea-pig ileum dose-dependently. (4) MLT (10,20,40 mg/kg,given for 8 days at the same with the administered of morphine ,twice a day.) inhibited the weight loss and withdrawl jumping significantly.(5) MLT (100,200,400μmol/l, administered 30 min prior to the precipitation of naloxone)decreased the withdrawl contraction significantly.(6) MLT (40,80mg/kg, ip ,30 min prior to the precipitation of naloxone) inhibited the jumping of morphine-dependent mice and decreased the weight loss significantly.(7) MLT (20 mg/kg,ip for 8 days ,twice a day.) could improve POMC mRNA of Arc translating into POMC and promote POMC degrading intoβ-EP. Also,it could make β-EP release to PAG and so it can inhibite the jumping of morphine-dependent mice and decreased the weight loss significantly.(8) MLT (80 mg/kg,ip once.) could promote the release of β-EP in Arc and increase the volume of β-EP in PAG, so it also can inhibite the jumping of morphine-dependent mice and decreased the weight loss .Conclusions: ① MLT dose not produce dependence on the GPI or mice. ②MLT (administered previously) can inhibit the development of morphine-dependence on the GPI or mice. ③MLT (administered acutly)can attenuate the withdrawl syndromes of morphine-dependence on the GPI or mice. ④ MLT (administered previously) can improve the synthesization of β-EP in Arc and promote it releasing to PAG, which may be one of mechanisms of the anti-morphine-dependence action of it. ⑤ MLT (administered acutly) can promote the release of β-endorphin in Arc and increase the volume of β-endorphin in PAG, which may be one of the mechanisms of anti-withdrawl-syndromes action .