Adolescent cocaine 5-HT3 Receptors and Aggression

描述（由申请人提供）： 拟议的研究的重点是检查血清素3型受体（5-HT 3r）在青少年可卡因促进攻击性攻击中的作用。已经观察到，皮质醇对几种神经递质系统有不同的影响，从而影响这些系统所服务的行为状态。5-羟色胺3型受体直接受到可卡因的影响，因此可能是促进这种滥用药物的行为效应的直接作用机制。我之前的研究已经将这种刺激受体定位于与攻击控制有关的几个大脑区域，包括下丘脑前部、终纹床核、内侧杏仁核和外侧隔。由申办研究者提供的证据表明，在攻击性的青少年可卡因治疗动物中，这些脑区的多巴胺能神经支配减少，因此需要研究5-HT 3r在该现象中的作用。在这个提议中概述的实验的目标是1）操纵可卡因促进的攻击性攻击与药理学药物，专门针对5-HT 3r和2）提供一个更完整的模型的电路调节青少年可卡因促进的攻击性通过表征可卡因暴露如何以及是否影响这个受体。在拟议的实验中观察到的结果将提供一个更好的理解在年轻人中观察到的异常行为和风险因素诱发年轻人的暴力行为导致实验可卡因的使用。

DESCRIPTION (provided by applicant): The focus of the proposed research is to examine the role of the serotonin type-3 receptor (5-HT3r) in adolescent cocaine facilitated offensive aggression. Cocaine has been observed to differentially effect several neurotransmitter systems and consequently behavioral states subserved by these systems. The serotonin type-3 receptor is affected directly by cocaine and thus may serve as a direct mechanism of action facilitating the behavioral effects of this abused drug. My previous research has localized this stimulatory receptor to several brain areas implicated in aggression control including the anterior hypothalamus, the bed nucleus of the stria terminalis, the medial amygdala and the lateral septum. Evidence, provided by the sponsoring investigator, of decreased serotonergic innervation of these brain areas in aggressive, adolescent cocaine treated animals warrants the investigation of the 5-HT3r's role in this phenomenon. The goals of the experiments outlined in this proposal are 1) to manipulate cocaine-facilitated offensive aggression with pharmacological agents that specifically target the 5-HT3r and 2) to provide a more complete model of the circuitry regulating adolescent cocaine-facilitated aggression by characterizing how and if cocaine exposure affects this receptor. Findings observed in the proposed experiments will provide a better understanding of the aberrant behaviors observed in young adults and the risk factors predisposing the young to violent behavior resulting from experimental cocaine use.