Behavioral Neurobiology of Aggression

攻击行为神经生物学

• 批准号: 7103420
• 负责人: KLAUS A MICZEK
• 金额: $ 46.6万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103420
• 关键词: Saimiri; aggression; alcoholic beverage consumption; alcoholism /alcohol abuse; gamma aminobutyrate; high performance liquid chromatography; impulsive behavior; laboratory mouse; laboratory rat; microdialysis; microinjections; neurochemistry; neuropsychological tests; neuropsychology; neuroregulation; neurotransmitter receptor; neurotransmitter transport; psychopharmacology; serotonin; social dominance; species difference; statistics /biometry; substance abuse related behavior

DESCRIPTION (provided by applicant): Epidemiological and criminal statistics as well as neurobiology, and pharmacotherapy all provide converging evidence that suggests links between alcohol consumption, impulsivity, and pathological aggression. The proposed research aims to dissect these links at the behavioral and neurochemical level, with particular focus on the relative role and interactions between GABAA and serotonin systems. A first specific aim seeks to analyze how alcohol-heightened aggression is related to other forms of escalated aggression. Experiments are designed to test the hypothesis whether or not a common behavioral profile of varied forms of escalated aggression characterizes individuals who engage in alcohol-heightened aggression. The second and third aims focus on pharmacological tools that are employed to characterize the relative contribution of 5-HT1A, 5-HT1B, and GABAA receptors, their pre- versus post-synaptic sites in brainstem, and prefrontal cortical regions in animals that engage in alcohol-heightened aggression. The fourth aim examines how serotonergic modulation of GABAergic systems determines alcohol-heightened aggression. Inversely, how do neuropharmacological manipulations of the modulatory sites on the GABAA receptor, particularly via neurosteroids, enable 5-HT-mediated effects on aggressive behavior? Pharmacological experiments are designed to stimulate pre-synaptically 5-HT1A and 5-HT1B receptors or to neurotoxically lesion raphe nuclei in order to assess the importance of serotonergic inhibition on the activating effects of positive modulators like neurosteroids on alcohol-heightened aggression. A fifth aim is directed at the neural sites of the GABAergic and serotonergic mechanisms that are critical for the aggression-heightening effects of alcohol. Intracranial microinjections are used to determine whether activation of 5-HT receptors in the raphe nucleus or in terminal forebrain regions are the critical sites for reducing escalated fighting. Conversely, can blockade of the 5-HT autoreceptors in the raphe n. potentiate the aggression-heightening effects of alcohol and other positive modulators at GABAA receptors? Additional evidence will be obtained by in vivo microdialysis experiments, in order to learn whether behavioral changes are reflected in significant changes in the level of GABA and serotonin release in cortico-limbic and brainstem areas.

描述（由申请人提供）：流行病学和犯罪统计以及神经生物学和药物治疗都提供了一致的证据，表明饮酒、冲动和病理性攻击之间存在联系。 拟议的研究旨在从行为和神经化学水平剖析这些联系，特别关注 GABAA 和血清素系统之间的相对作用和相互作用。第一个具体目标是分析酒精导致的攻击行为与其他形式的攻击行为升级之间的关系。实验旨在检验这一假设，即各种形式的升级攻击行为的共同行为特征是否是酒精加剧攻击行为的个体的特征。第二个和第三个目标侧重于药理学工具，用于表征 5-HT1A、5-HT1B 和 GABAA 受体的相对贡献、它们在脑干中的突触前位点与突触后位点以及参与酒精增强攻击性的动物的前额皮质区域。 第四个目标是研究 GABA 系统的血清素调节如何决定酒精增强的攻击性。相反，对 GABAA 受体调节位点的神经药理学操作（特别是通过神经类固醇）如何使 5-HT 介导的攻击行为发挥作用？药理学实验旨在刺激突触前 5-HT1A 和 5-HT1B 受体或神经毒性损伤中缝核，以评估血清素能抑制对正调节剂（如神经类固醇）对酒精增强攻击性的激活作用的重要性。第五个目标针对 GABA 能和血清素能机制的神经部位，这些部位对于酒精增强攻击性的作用至关重要。颅内显微注射用于确定中缝核或末端前脑区域 5-HT 受体的激活是否是减少战斗升级的关键部位。 相反，可以阻断中缝中的 5-HT 自身受体。增强酒精和其他正调节剂对 GABAA 受体的攻击性增强作用？体内微透析实验将获得更多证据，以了解行为变化是否反映在皮质边缘和脑干区域 GABA 和血清素释放水平的显着变化上。