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托莫西汀对猴子的强化作用评估:与哌甲酯及地昔帕明的比较。

Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine.

作者信息

Wee Sunmee, Woolverton William L

机构信息

Department of Psychiatry and Human Behavior, Division of Neurobiology and Behavior Research, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.

出版信息

Drug Alcohol Depend. 2004 Sep 6;75(3):271-6. doi: 10.1016/j.drugalcdep.2004.03.010.

Abstract

Atomoxetine is a selective norepinephrine (NE) reuptake blocker that has recently been marketed for the treatment of attention deficit hyperactivity disorder. The purpose of the present study was to evaluate the self-administration of atomoxetine in an animal model predictive of abuse liability in humans. Rhesus monkeys (N = 5) were prepared with chronic intravenous catheters and allowed to self-administer cocaine or saline during alternating baseline sessions. When behavior was stable, atomoxetine (0.03-3.0 mg/kg per injection), desipramine (0.1-3.0 mg/kg per injection), methylphenidate (0.001-0.1 mg/kg per injection), or their vehicles were substituted for baseline conditions. Methylphenidate consistently maintained responding above the levels maintained by its vehicle. Atomoxetine and desipramine failed to reliably maintain self-administration above vehicle levels in four of five individual monkeys. These results predict that atomoxetine, in contrast to methylphenidate but like desipramine, will lack reinforcing effects and abuse potential in humans.

摘要

托莫西汀是一种选择性去甲肾上腺素(NE)再摄取阻滞剂,最近已上市用于治疗注意力缺陷多动障碍。本研究的目的是在一种可预测人类滥用可能性的动物模型中评估托莫西汀的自我给药情况。给5只恒河猴植入慢性静脉导管,在交替的基线期让它们自我给药可卡因或生理盐水。当行为稳定后,用托莫西汀(每次注射0.03 - 3.0毫克/千克)、地昔帕明(每次注射0.1 - 3.0毫克/千克)、哌甲酯(每次注射0.001 - 0.1毫克/千克)或它们的溶媒替代基线条件。哌甲酯始终使反应维持在其溶媒所维持的水平之上。在五只个体猴子中的四只中,托莫西汀和地昔帕明未能可靠地使自我给药维持在溶媒水平之上。这些结果预测,与哌甲酯不同但与地昔帕明相似,托莫西汀在人类中将缺乏强化作用和滥用潜力。

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