Anhydroecgonine methyl ester (AEME), also called methylecgonidine, is a pyrolysis product of crack cocaine that is neurotoxic and potentiates cocaine-induced sensitization. The sensitization induced by drugs of abuse can be influenced by melatonin, a neuroprotective pineal hormone. In the same way, drugs of abuse like alcohol and methamphetamine can modify melatonin synthesis. The aim of the present work was to investigate the AEME effects on melatonin synthesis in the rat pineal gland. Neurotransmitter systems involved in its effects, antioxidant enzyme activities and the melatonin protective role in AEME-induced toxicity were also evaluated. The animals were injected with AEME i.p. (1.12 mg per kg of body weight per day) or vehicle for 10 consecutive days and the nocturnal pineal melatonin synthesis profile and SOD, GPx and GR activities in the cerebral cortex and hippocampus were assessed. Cultured pineal glands were incubated with AEME for 30 min or 48 h before norepinephrine stimulation and melatonin synthesis, arylalkylamine N-acetyltransferase activity, cAMP and [Ca2+]i were determined. The involvement of cholinergic and glutamatergic systems was analyzed using different antagonists. The protective role of melatonin in AEME toxicity on hippocampal neurons was evaluated by a viability assay. AEME impaired melatonin synthesis both in vivo and in vitro and this effect seems to be mediated by muscarinic receptors and [Ca2+]i elevation. AEME reduced neuronal viability and melatonin was able to protected hippocampal neurons against AEME toxicity. The melatonin synthesis impairment observed could lead to the worsening of the direct AEME neurotoxicity and to the exacerbation of the crack cocaine addiction and sensitization.

中文翻译：

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脱水芽子碱甲酯（一种可卡因热解产物）的毒蕈碱作用会损害大鼠松果体中褪黑激素的合成。


脱水芽康宁甲酯 (AEME)，也称为甲基芽康定，是强效可卡因的热解产物，具有神经毒性，可增强可卡因诱导的致敏作用。滥用药物引起的过敏可能会受到褪黑激素（一种神经保护性松果体激素）的影响。同样，酒精和甲基​​苯丙胺等滥用药物也会改变褪黑激素的合成。本工作的目的是研究 AEME 对大鼠松果体褪黑激素合成的影响。还评估了涉及其作用的神经递质系统、抗氧化酶活性和褪黑激素在 AEME 诱导的毒性中的保护作用。连续10天给动物腹腔注射AEME（每天每公斤体重1.12毫克）或媒介物，并评估夜间松果体褪黑激素合成概况以及大脑皮层和海马中的SOD、GPx和GR活性。将培养的松果体与 AEME 一起孵育 30 分钟或 48 小时，然后测定去甲肾上腺素刺激和褪黑激素合成、芳基烷基胺 N-乙酰转移酶活性、cAMP 和 [Ca2+]i。使用不同的拮抗剂分析胆碱能和谷氨酸能系统的参与。通过活力测定评估褪黑激素在 AEME 对海马神经元毒性中的保护作用。 AEME 损害了体内和体外褪黑激素的合成，这种效应似乎是由毒蕈碱受体和 [Ca2+]i 升高介导的。 AEME 降低了神经元活力，褪黑激素能够保护海马神经元免受 AEME 毒性。观察到的褪黑激素合成障碍可能导致直接 AEME 神经毒性的恶化以及强效可卡因成瘾和致敏的加剧。