Mitchell Heather A, Ahern Todd H, Liles L Cameron, Javors Martin A, Weinshenker David
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
Biol Psychiatry. 2006 Nov 15;60(10):1046-52. doi: 10.1016/j.biopsych.2006.03.057. Epub 2006 Aug 7.
Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity.
Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded.
Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice.
Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.
急性给予不同类别的抗抑郁药可增强或降低新环境中的自发运动活性，但慢性抗抑郁治疗对新环境和熟悉环境中自发运动活性的影响尚不明确。由于去甲肾上腺素是自发运动活性的重要调节因子，我们推测去甲肾上腺素转运体阻断作用有助于某些抗抑郁药对自发运动活性产生影响。
将抗抑郁药（瑞波西汀、地昔帕明、丙咪嗪、文拉法辛、安非他酮）急性（腹腔注射）或慢性（通过渗透微型泵）给予对照小鼠和去甲肾上腺素转运体基因敲除小鼠，并记录新环境或熟悉环境中的自发运动活性。
大多数阻断去甲肾上腺素转运体的抗抑郁药急性治疗可降低新环境中的自发运动活性，而慢性治疗则可降低新环境和熟悉环境中的自发运动活性。例外的是安非他酮，一种双重去甲肾上腺素转运体/多巴胺转运体阻断剂，它倾向于增加自发运动活性。瑞波西汀与多巴胺转运体阻断剂GBR 12909联合给药也可增加自发运动活性。去甲肾上腺素转运体基因敲除小鼠的基础自发运动活性较低，安非他酮可使其增加，而瑞波西汀对去甲肾上腺素转运体基因敲除小鼠无影响。
除非与多巴胺转运体阻断作用相结合，去甲肾上腺素转运体的急性或慢性失活会降低新环境和熟悉环境中的自发运动活性。
