RATIONALE MK801, like other NMDA receptor open-channel blockers (e.g., ketamine and phencyclidine), increases the locomotor activity of rats and mice. Whether this behavioral effect ultimately relies on monoamine neurotransmission is of dispute. OBJECTIVE The purpose of this study was to determine whether these psychopharmacological effects and underlying neural mechanisms vary according to sex and age. METHODS Across four experiments, male and female preweanling and adolescent rats were pretreated with vehicle, the monoamine-depleting agent reserpine (1 or 5 mg/kg), the dopamine (DA) synthesis inhibitor ∝-methyl-DL-p-tyrosine (AMPT), the serotonin (5-HT) synthesis inhibitor 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), or both AMPT and PCPA. The locomotor activity of preweanling and adolescent rats was then measured after saline or MK801 (0.3 mg/kg) treatment. RESULTS As expected, MK801 increased the locomotor activity of all age groups and both sexes, but the stimulatory effects were significantly less pronounced in male adolescent rats. Preweanling rats and adolescent female rats were more sensitive to the effects of DA and 5-HT synthesis inhibitors, as AMPT and PCPA caused only small reductions in the MK801-induced locomotor activity of male adolescent rats. Co-administration of AMPT+PCPA or high-dose reserpine (5 mg/kg) treatment substantially reduced MK801-induced locomotor activity in both age groups and across both sexes. CONCLUSIONS These results, when combined with other recent studies, show that NMDA receptor open-channel blockers cause pronounced age-dependent behavioral effects that can vary according to sex. The neural changes underlying these sex and age differences appear to involve monoamine neurotransmission.

中文翻译：

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MK801 诱导的断奶前和青春期雄性和雌性大鼠的运动活动：多巴胺和血清素系统的作用。

原理 MK801 与其他 NMDA 受体开放通道阻滞剂（例如，氯胺酮和苯环利定）一样，可增加大鼠和小鼠的运动活性。这种行为效应是否最终依赖于单胺神经传递是有争议的。目的 本研究的目的是确定这些精神药理作用和潜在的神经机制是否因性别和年龄而异。方法 在四个实验中，雄性和雌性断奶前和青春期大鼠用载体、单胺消耗剂利血平（1 或 5 mg/kg）、多巴胺 (DA) 合成抑制剂∝-甲基-DL-p-酪氨酸 (AMPT) 预处理)、血清素 (5-HT) 合成抑制剂 4-氯-DL-苯丙氨酸甲酯盐酸盐 (PCPA)，或 AMPT 和 PCPA。然后在生理盐水或 MK801 (0.3 mg/kg) 治疗后测量断奶前和青春期大鼠的运动活动。结果 正如预期的那样，MK801 增加了所有年龄组和两性的运动活动，但刺激作用在雄性青春期大鼠中明显不那么明显。断奶前大鼠和青春期雌性大鼠对 DA 和 5-HT 合成抑制剂的影响更敏感，因为 AMPT 和 PCPA 仅导致雄性青春期大鼠的 MK801 诱导的运动活性小幅降低。AMPT+PCPA 或高剂量利血平 (5 mg/kg) 的共同给药显着降低了 MK801 诱导的两个年龄组和两个性别的运动活动。结论 这些结果，当与其他最近的研究相结合时，表明 NMDA 受体开放通道阻滞剂会导致明显的年龄依赖性行为影响，这些影响可能因性别而异。这些性别和年龄差异背后的神经变化似乎涉及单胺神经传递。