Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA.
Neurosci Lett. 2012 May 10;516(1):99-104. doi: 10.1016/j.neulet.2012.03.066. Epub 2012 Apr 1.
Methadone is a synthetic opiate that is useful in a variety of clinical settings, including in maintenance therapy of heroin dependence and as an analgesic. However, methadone can have negative effects on cognition in humans and in rodents. The mechanisms underlying methadone-induced disruption in cognition are unknown. One possibility is that methadone disrupts adult hippocampal neurogenesis, a form of hippocampal plasticity involved in cognition that is disrupted by other opiates, like morphine. The goal of this study was to determine if methadone alters key parameters of hippocampal neurogenesis in the adult rat. Four groups of male rats were injected with saline (Saline, n=11) or methadone (Escalating, Short Term, Acute, n=10-11/group) over the course of three weeks. Weight gain, locomotor activity, and neurogenesis data were collected. Consistent with prior results, Escalating rats had slower weight gain (-4% vs. Saline). Also consistent with prior results, methadone did not alter locomotor activity over the course of a 90 min test. However, closer analysis revealed that methadone - irrespective of the dose or duration - led to a decrease in locomotor activity (-11 to -20% vs. saline) when examined during the first 5 min of the locomotor test. Surprisingly, methadone did not alter any of three quantified parameters relevant to adult hippocampal neurogenesis (number of Ki67-, doublecortin-, or BrdU-immunoreactive cells [BrdU given prior to saline/methadone exposure]). These results suggest that - unlike other opiates such as morphine - experimenter-delivered methadone does not alter hippocampal plasticity by decreasing the number of adult-generated neurons.
美沙酮是一种合成阿片类药物，在多种临床环境中都有应用，包括海洛因依赖的维持治疗和作为镇痛药。然而，美沙酮会对人类和啮齿动物的认知产生负面影响。美沙酮引起认知障碍的机制尚不清楚。一种可能性是，美沙酮破坏了成年海马神经发生，这是一种与认知有关的海马可塑性形式，其他阿片类药物，如吗啡，会破坏这种可塑性。本研究的目的是确定美沙酮是否会改变成年大鼠海马神经发生的关键参数。四组雄性大鼠连续三周分别接受生理盐水（生理盐水组，n=11）或美沙酮（递增组、短期组、急性组，n=10-11/组）注射。收集体重增加、运动活动和神经发生数据。递增组大鼠体重增加缓慢（-4% vs. 生理盐水组），与之前的结果一致。与之前的结果一致，美沙酮在 90 分钟测试过程中没有改变运动活动。然而，更仔细的分析表明，无论剂量或持续时间如何，美沙酮都会导致运动测试前 5 分钟内运动活动减少（-11%至-20% vs. 生理盐水）。令人惊讶的是，美沙酮没有改变与成年海马神经发生相关的三个量化参数中的任何一个（Ki67、双皮质素或 BrdU 免疫反应性细胞的数量[BrdU 在生理盐水/美沙酮暴露之前给予]）。这些结果表明，与其他阿片类药物（如吗啡）不同，实验给予的美沙酮不会通过减少成年产生的神经元数量来改变海马可塑性。
