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

该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作用 并确定可能具有治疗价值的药物 兴奋剂滥用 方法将计划控制的行为作为 中枢神经系统活动指数，静脉自我给药， 表明增强功效或滥用倾向的药物， 控制行为的区别性刺激和体内微透析 技术允许测量直接神经化学 与药物对行为的影响有关的变化。 期间的努力 在过去的一年里，人们关注的是药物对 5-羟色胺系统，以评估对CNS效应的敏感性变化 可卡因。 给予增加肾上腺素能的药物 活动可靠地减弱了行为刺激和强化 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抑制调节 具有选择性多巴胺能作用的兴奋剂。 后者的结果 表明可卡因和相关滥用药物的多巴胺能调节 兴奋剂可能涉及血清素和 多巴胺 皮质醇和相关的多巴胺转运阻滞剂也会引起 细胞外多巴胺的显著增加， 作用时程与药物引起的变化密切相关 在时间表控制的操作性行为。 这些数据共同 表明血清素系统可能是一个有效的目标， 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.