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以及药物治疗都提供了融合的证据，这表明饮酒，冲动性和病理侵略性之间有联系。 拟议的研究旨在在行为和神经化学层面上剖析这些联系，尤其关注GABAA和5-羟色胺系统之间的相对作用和相互作用。第一个特定的目的旨在分析酒精高侵略与其他形式的侵略性相关。实验旨在检验假设，是否表征参与酒精高侵略的个体的各种形式的越来越多形式的行为概况。第二和第三旨在侧重于用于表征5-HT1A，5-HT1B和GABAA受体的相对贡献的药理学工具，它们在脑干中的前突触部位和前突触部位以及动物前额叶皮质区域的相对贡献。 第四目的是研究GABA能系统的血清素能调节如何决定饮酒侵略。相反，如何对GABAA受体（尤其是通过神经固醇）上调节位点的神经药理操纵如何产生5-HT介导的对攻击行为的影响？设计的药理实验旨在刺激突触前的5-HT1A和5-HT1B受体或神经毒性病变的Raphe核，以评估血清素能抑制对神经类固醇（如神经类固醇对酒精强化攻击）阳性调节剂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，这对于酒精的侵略性高度影响至关重要。颅内显微注射用于确定Raphe核中5-HT受体的激活是否是减少升级战斗的关键部位。 相反，可以阻止Raphe n中的5-HT自动受体。增强酒精和其他正调节剂对GABAA受体的侵略性高度影响？为了了解Cortico-Limbic和脑干地区GABA和5-羟色胺释放水平的重大变化，体内微透析实验将获得其他证据。