BEHAVIORAL & PHYSIOLOGICAL CONCOMITANTS OF DRUG ABUSE:COCAINE: 5HT

这个项目的长期目标是描述 可卡因对非人灵长类动物的行为和神经化学影响 并确定在治疗中可能具有治疗价值的药物 兴奋剂滥用。方法包括计划控制的行为作为 中枢神经系统活动指数、静脉给药情况 表明增强疗效或滥用倾向的药物，如 辨别性刺激控制行为与体内微透析 允许测量直接神经化学物质的技术 与药物对行为的影响相关的变化。在此期间所做的努力 在过去的一年里，他们专注于药物操纵 5-羟色胺系统评估中枢神经系统敏感性的变化 可卡因。增加5-羟色胺能的药物的使用 活动可靠地减弱了行为刺激剂并增强了 可卡因的影响。此外，药物相互作用研究表明， 5-羟色胺系统可以提供精神运动的抑制调制。 具有选择性多巴胺能作用的兴奋剂。后一种结果 提示可卡因的5-羟色胺能调制及相关滥用 兴奋剂可能涉及5-羟色胺和5-羟色胺 多巴胺。可卡因和相关的多巴胺转运阻滞剂也会导致 细胞外多巴胺显著增加，药物效力 作用的时间进程与药物引起的变化密切相关 在时间表控制的操作行为中。总的来说，这些数据 提示5-羟色胺系统可能是一个有效的靶点 可卡因滥用的治疗。

The long-range objective of this project is to characterize the behavioral and neurochemical effects of cocaine in nonhuman primates and to identify drugs that may have therapeutic value in treating stimulant abuse. Methods include schedule-controlled behavior as an index of CNS activity, intravenous self-administration of drugs as indicative of reinforcing efficacy or abuse liability, drugs as discriminative stimuli controlling behavior, and in vivo microdialysis techniques to allow for the measurement of direct neurochemical changes associated with drug effects on behavior. Efforts during the past year have focused on pharmacological manipulation of the serotonin system to assess changes in sensitivity to the CNS effects of cocaine. Administration of drugs that increase serotonergic activity reliably attenuated the behavioral-stimulant and reinforcing effects of cocaine. Moreover, drug interaction studies indicated that the serotonin system can provide inhibitory modul ation of psychomotor stimulants with selective dopaminergic actions. The latter results suggest that serotonergic modulation of cocaine and related abused stimulants may involve direct interactions between serotonin and dopamine. Cocaine and related dopamine transport blockers also caused pronounced increases in extracellular dopamine, and the drug potency and time course of action corresponded closely to drug-induced changes in schedule-controlled operant behavior. Collectively, these data indicate that the serotonin system may be an effective target for the treatment of cocaine abuse.