Evaluation of the 5-HT2C agonist lorcaserin as potential treatment for cocaine ab

描述（由申请人提供）：滥用药物的积极强化特性被认为是由于中边缘多巴胺（DA）系统活性增强所致。除了经典和非典型抗精神病药物直接阻断DA传递外，另一种降低中枢DA活性的方法是通过刺激5-羟色胺5-HT2C受体。本提案中描述的研究将评估一种这样的5-HT2C激动剂氯卡色林，它已经在其他适应症的临床开发中取得了很好的进展，用于减少恒河猴的可卡因滥用相关行为。在这种非人类灵长类动物（NHP）中获得的数据应该比在啮齿动物中获得的数据更能预测人类的临床效果。目的是确定NHP的数据是否会为氯卡色林治疗人类可卡因滥用的临床试验提供鼓励。实验将评估氯卡色林对可卡因引起的多动症的衰减作用；在药物鉴别过程中，可卡因保持了自我给药行为和可卡因的内部刺激特性。为了证明氯卡色林可能对治疗人类可卡因滥用有用，这些实验应该表明，氯卡色林在剂量下有效地减轻NHP患者的可卡因滥用相关行为，而不会对行为产生内在影响。

DESCRIPTION (provided by applicant): The positive reinforcing properties of drugs of abuse are thought to result from enhanced activity in meso-limbic dopamine (DA) systems. In addition to direct blockade of DA transmission by classical and atypical antipsychotics, an alternative approach to diminishing central DA activity is via stimulation of serotonin 5-HT2C receptors. The research described in the present proposal will evaluate one such 5-HT2C agonist lorcaserin, already well advanced in clinical development in other indications, for its attenuation of cocaine abuse-related behavior in the rhesus monkey. Data obtained in this non-human primate (NHP) should better predict clinical effects in humans than data from rodents. The aim is to determine whether the NHP data would provide encouragement, or not, for the clinical testing of lorcaserin for treating cocaine abuse in humans. The experiments will evaluate lorcaserin for attenuation of cocaine-induced hyperactivity; cocaine maintained self-administration behavior and the internal stimulus properties of cocaine in a drug discrimination procedure. To demonstrate that lorcaserin could be useful for treating cocaine abuse in humans, these experiments should show that lorcaserin is effective in attenuating cocaine abuse- related behavior in NHP at doses without intrinsic effects on behavior.