Adolescent cocaine 5-HT3 Receptors and Aggression

描述(由申请人提供)： 这项拟议的研究的重点是检查5-羟色胺3型受体(5-HT3r)在青少年可卡因促进攻击性攻击中的作用。可卡因已经被观察到对几个神经递质系统有不同的影响，因此这些系统所支持的行为状态。5-羟色胺3型受体直接受可卡因的影响，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性受体定位于几个与攻击控制有关的脑区，包括下丘脑前部、终纹床核、杏仁内侧核和外侧隔核。赞助研究人员提供的证据表明，在攻击性的青少年可卡因治疗的动物中，这些大脑区域的5-羟色胺能神经支配减少，这证明了5-HT3r在这一现象中的作用。这项提议中概述的实验的目标是：1)用专门针对5-HT3r的药理药物操纵可卡因促成的攻击性攻击；2)通过表征可卡因暴露如何以及是否影响这一受体，提供调控青少年可卡因促成攻击的回路的更完整的模型。在拟议的实验中观察到的结果将有助于更好地了解在年轻人中观察到的异常行为，以及导致年轻人因实验性可卡因使用而产生暴力行为的危险因素。

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.