Department of Psychology, California State University, San Bernardino, CA, USA.
Department of Psychology, California State University, San Bernardino, CA, USA; Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Behav Brain Res. 2020 Feb 3;379:112267. doi: 10.1016/j.bbr.2019.112267. Epub 2019 Oct 5.
Ketamine significantly increases the locomotor activity of rodents, however this effect varies according to the sex and age of the animal being tested. To determine the role monoamine systems play in ketamine's locomotor activating effects: (a) male and female preweanling, adolescent, and adult rats were pretreated with vehicle or the monoamine depleting agent reserpine (1 or 5 mg/kg), and (b) the behavioral actions of ketamine (20 or 40 mg/kg) were then compared to d-amphetamine (2 mg/kg) and cocaine (10 or 15 mg/kg). The ability of reserpine to deplete dorsal striatal dopamine (DA) and serotonin (5-HT) in male and female rats was determined using HPLC. Ketamine caused substantial increases in the locomotion of preweanling rats and older female rats (adolescents and adults), but had only small stimulatory effects on adolescent and adult male rats. When compared to cocaine and d-amphetamine, ketamine was especially sensitive to the locomotor-inhibiting effects of monoamine depletion. Ketamine-induced locomotion is at least partially mediated by monoamine systems, since depleting DA and 5-HT levels by 87-96% significantly attenuated the locomotor activating effects of ketamine in male and female rats from all three age groups. When administered to reserpine-pretreated rats, ketamine produced a different pattern of behavioral effects than either psychostimulant, suggesting that ketamine does not stimulate locomotor activity via actions at the presynaptic terminal. Instead, our results are consistent with the hypothesis that ketamine increases locomotor activity through a down-stream mechanism, possibly involving ascending DA and/or 5-HT projection neurons.
氯胺酮显著增加啮齿动物的运动活动，但这种作用因被测试动物的性别和年龄而异。为了确定单胺系统在氯胺酮的运动激活作用中的作用：（a）雄性和雌性未成熟、青春期和成年大鼠用载体或单胺耗竭剂利血平（1 或 5mg/kg）预处理，然后（b）比较氯胺酮（20 或 40mg/kg）的行为作用与 d-苯丙胺（2mg/kg）和可卡因（10 或 15mg/kg）。使用 HPLC 确定利血平在雄性和雌性大鼠中耗竭背侧纹状体多巴胺（DA）和 5-羟色胺（5-HT）的能力。氯胺酮导致未成熟大鼠和老年雌性大鼠（青春期和成年）的运动活动大幅增加，但对青春期和成年雄性大鼠的刺激作用很小。与可卡因和 d-苯丙胺相比，氯胺酮对单胺耗竭的运动抑制作用特别敏感。氯胺酮诱导的运动至少部分由单胺系统介导，因为通过 87-96%耗竭 DA 和 5-HT 水平显著减弱了来自所有三个年龄组的雄性和雌性大鼠的氯胺酮的运动激活作用。当给予利血平预处理的大鼠时，氯胺酮产生的行为效应模式与任何一种精神兴奋剂都不同，这表明氯胺酮不是通过突触前终端的作用刺激运动活动。相反，我们的结果与氯胺酮通过下游机制增加运动活动的假设一致，可能涉及上行 DA 和/或 5-HT 投射神经元。
