Adolescent cannabinoid exposure in a rodent model of schizophrenia susceptibility

精神分裂症易感性啮齿动物模型中的青少年大麻素暴露

• 批准号: 8912000
• 负责人: David Dominguez Aguilar
• 金额: $ 2.98万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912000
• 关键词: Adolescence; Adolescent; Affect; Animal Disease Models; Animal Model; Animals; Area; Behavior; Behavioral; Calcium-Binding Proteins; Cannabinoids; Cannabis; Cannabis Abuse; Chronic; Clinical Data; Cognitive deficits; Control Animal; Data; Development; Dopamine; Dose; Electrophysiology (science); Environmental Risk Factor; Ethics; Experimental Designs; Fathers; Future; Generations; Genetic; Genetic Predisposition to Disease; Genetic Risk; Hippocampus (Brain); Human; Individual; Inherited; Interneurons; Investigational Therapies; Laboratories; Measures; Mental disorders; Methylazoxymethanol Acetate; Modeling; Molecular; Mothers; Neurons; Parvalbumins; Phenotype; Population; Predisposition; Rattus; Receptor Activation; Research Personnel; Risk; Risk Factors; Rodent; Rodent Model; Schizophrenia; Social Interaction; Symptoms; Techniques; Training; Treatment Protocols; Ventral Tegmental Area; adolescent patient; cannabinoid receptor; career; dopamine system; dopaminergic neuron; gene environment interaction; in vivo; male; marijuana use; marijuana user; neurochemistry; neurophysiology; novel; preclinical study; psychotic symptoms; public health relevance; skills; synthetic cannabinoid; transmission process

 DESCRIPTION (provided by applicant): This project aims to explore the interaction of genetic and environmental factors in the development of psychotic symptoms. Cannabinoid exposure during adolescence is associated with an increased risk of developing schizophrenia, but this correlation is not causative. Thus, it is likely that people with a genetic predisposition to psychotic symptoms are more strongly affected by environmental risk factors. We have developed an animal model with increased susceptibility to schizophrenia-like symptoms by using the second filial (F2) generation of rats that were developmentally disrupted with methylazoxymethanol acetate (MAM). We hypothesize cannabinoid exposure during adolescence will increase the proportion of these "F2 MAM" rats displaying a schizophrenia-like phenotype. This phenotype will be evaluated at the behavioral level (with stimulant-induced hyperlocomotion, social interaction, and attentional set-shifting), the cellular level (spontaneous dopamine neuron activity and hippocampal pyramidal activity), and the molecular level (expression of inhibitory markers). Understanding additive or interactive effects of risk factors could allow us to make more accurate predictions of developing psychotic symptoms, as well as personalize warnings for those already at risk. Furthermore, a model of susceptibility would be extremely useful for preventative experimental therapies. This proposal will provide important training in experimental design, laboratory and analytical techniques, ethics, and other essential skills for a future independent investigator.

 描述（由适用提供）：该项目旨在探讨遗传和环境因素在精神病症状发展中的相互作用。青少年期间大麻素暴露与患有精神分裂症的风险增加有关，但这种相关性并不严重。这样，患有遗传易感性症状的人可能会受到环境危险因素的强烈影响。我们通过使用第二份申请（F2）生成大鼠的动物模型，对精神分裂症样症状的敏感性增加，这些大鼠被乙酸甲酯（MAM）开发和破坏。我们假设在青少年期间的大麻素暴露会增加这些“ F2 MAM”大鼠的比例，这些“ F2 MAM”大鼠表现出类似精神分裂症的表型。该表型将在行为水平上进行评估（具有刺激性诱导的超倒置，社交相互作用和注意力设置转换），该表型（自发） 多巴胺神经元活性和海马锥体活性）和分子水平（抑制标记的表达）。了解风险因素的添加剂或互动效应可能会使我们能够对患有精神病症状进行更准确的预测，并为已经处于危险的人们提供个性化警告。此外，一种易感性模型对于预防实验疗法将非常有用。该建议将为未来独立研究者提供实验设计，实验室和分析技术，道德和其他基本技能的重要培训。