Wei Yi-Ming, Xu Ying, Yu Chang-Xi
Department of Pharmacology, Fujian Medical University, Fuzhou 350004, China.
Sheng Li Xue Bao. 2007 Dec 25;59(6):765-9.
The present study was undertaken to investigate the effect of melatonin on the content of β-endorphin (β-EP) in the hypothalamic arcuate nucleus (Arc) and periaqueductal grey (PAG) of midbrain in morphine withdrawal mice. Male Kunming mice were injected subcutaneously (s.c.) with an increasing dose of morphine continuously for 8 d to establish morphine dependence model. Withdrawal response was induced by naloxone (3 mg/kg body weight, s.c.). The potency of withdrawal response was evaluated according to the jumping times and body weight loss. Ninty minutes prior to the precipitation of naloxone, 80 mg/kg body weight of melatonin (MEL) was injected intraperitoneally (i.p.) to observe its antagonistic effect on the withdrawal response in morphine-dependent mice. After behavioral observation, radioimmunoassay was used to determine the content of β-EP in the PAG of midbrain, and immunohistochemical assay was used to observe the intensity of β-EP-like immunoreactivity in the Arc in mice. It was shown that MEL inhibited the naloxone-precipitated withdrawal responses in mice significantly (P<0.05). In the meantime, MEL increased the content of β-EP in the PAG of midbrain significantly (P<0.05) and attenuated the intensity of β-EP-like immunoreactivity in the Arc in mice (P<0.05). The results suggest that MEL increases the content of β-EP in the PAG of midbrain, decrease the content of β-EP in the Arc in morphine withdrawal mice.
本研究旨在探讨褪黑素对吗啡戒断小鼠下丘脑弓状核（Arc）和中脑导水管周围灰质（PAG）中β-内啡肽（β-EP）含量的影响。雄性昆明小鼠连续8天皮下注射递增剂量的吗啡以建立吗啡依赖模型。用纳洛酮（3 mg/kg体重，皮下注射）诱发戒断反应。根据跳跃次数和体重减轻评估戒断反应的强度。在注射纳洛酮前90分钟，腹腔注射80 mg/kg体重的褪黑素（MEL），观察其对吗啡依赖小鼠戒断反应的拮抗作用。行为观察后，采用放射免疫分析法测定中脑PAG中β-EP的含量，采用免疫组织化学分析法观察小鼠Arc中β-EP样免疫反应的强度。结果表明，MEL显著抑制小鼠纳洛酮诱发的戒断反应（P<0.05）。同时，MEL显著增加中脑PAG中β-EP的含量（P<0.05），并减弱小鼠Arc中β-EP样免疫反应的强度（P<0.05）。结果提示，MEL增加吗啡戒断小鼠中脑PAG中β-EP的含量，降低Arc中β-EP的含量。
