LIMBIC MONOAMINES, BEHAVIOR, AND PSYCHOPATHOLOGY

边缘单胺、行为和心理病理学

• 批准号: 2240771
• 负责人: MARK A GEYER
• 金额: $ 8.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2240771
• 关键词: antipsychotic agents; attention; auditory stimulus; behavior test; behavioral habituation /sensitization; chordate locomotion; cognition disorders; conditioning; dopamine; ethology; evoked potentials; exploratory behavior; hallucinogens; human subject; isolation /deprivation; laboratory rat; neural inhibition; neuroanatomy; psychopharmacology; schizophrenia; sensorimotor system; sensory feedback; serotonin; serotonin receptor; startle reaction

This application for an ADAMHA Research Scientist Award follow,s ten years of NIMH support via the Type II Research Scientist Development Award. At the basic level, the project assesses the involvement of limbic dopaminergic, glutamatergic, and serotonergic systems in rats in the modulation of behavioral responsiveness to environmental stimuli. At the preclinical interface, the proposed experiments will further characterize deficits in sensorimotor gating and habituation observed in schizophrenic patients and extend related animal models derived from the basic studies. Schizophrenic patients exhibit deficits in prepulse inhibition of startle, gating of P3O event-related potentials, and habituation of startle. The proposed studies will: compare prepulse inhibition, P5O gating, and habituation functions in the same patients; relate these deficits to several clinical factors; and examine unmedicated schizophrenics, family members of schizophrenics, and schizotypal patients. In rats, prepulse inhibition of startle is reduced by D2 dopaminergic activation and by related manipulations of neuronal circuitry involving the hippo-campus, nucleus accumbens, ventral pallidum, and pedunculopontine nucleus. Prepulse inhibition is also disrupted by direct and indirect serotonin agonists, non-competitive antagonists at the N-methyl-d-aspartate receptor complex, and isolation rearing. The proposed studies will examine the psychopharmacology and neurobiological substrates relevant to this animal model of the schizophrenic deficit in sensorimotor gating. In rats, startle habituation is deceased by serotonin agonists and increased by serotonin antagonists. These serotonin agonist effects may provide a model of the schizophrenic deficit in habituation. Studies using a behavioral pattern monitor which provides a detailed profile of investigatory and locomotor behaviors, reveals that direct serotonin agonists similarly potentiate other measures of responsiveness to environmental stimuli. The release of presynaptic serotonin by indirect agonists reduces investigatory behavior while increasing locomotor activity. A variety of manipulations of serotonergic systems in rats are proposed to identify the receptor subtypes and, pathways involved in the serotonergic modulation of sensorimotor responsivity and behavioral activity.

该申请申请Adamha Research Scientist奖，如下十年 通过II型研究科学家发展奖的NIMH支持。在 基本级别，该项目评估了边缘的参与 大鼠多巴胺能，谷氨酸能和5-羟色胺能系统 调节对环境刺激的行为反应能力。在 临床前界面，提出的实验将进一步表征 在精神分裂症中观察到的感觉运动门控和习惯的缺陷 患者并扩展了从基础研究中得出的相关动物模型。 精神分裂症患者在抑制惊吓时表现出缺陷， P3O事件相关电位的门控和惊吓的习惯。这 拟议的研究将：比较预硫次抑制，p5O门控和 习惯在同一患者中起作用；将这些赤字与 几个临床因素；并检查未经药物的精神分裂症患者，家庭 精神分裂症患者和精神分裂症患者的成员。在大鼠中，预硫 D2多巴胺能激活减少了惊吓的抑制作用 涉及河马校园的神经元电路的相关操作， 伏隔核，腹侧粒细胞和小儿核核。 直接和间接的5-羟色胺也破坏了预硫的抑制作用 激动剂，N-甲基-D-天冬氨酸受体的非竞争拮抗剂 复杂和孤立饲养。拟议的研究将研究 与该动物相关的心理药理学和神经生物学基质 感觉运动门控中精神分裂症的模型。在老鼠中， 惊吓的习惯被5-羟色胺激动剂死亡，并增加了 5-羟色胺拮抗剂。这些5-羟色胺激动剂的作用可能会提供模型 习惯性精神分裂症的缺陷。使用行为的研究 模式监视器提供了调查和调查的详细概况 运动行为，揭示了类似的指导5-羟色胺激动剂 增强对环境刺激的反应性的其他措施。这 通过间接激动剂释放突触前5-羟色胺 研究行为同时增加运动活性。各种各样 提出了对大鼠血清素能系统的操纵，以识别 受体亚型和涉及血清素能调节的途径 感觉运动反应和行为活性。