Amphetamine sensitization in a model of schizophrenia

精神分裂症模型中的安非他明致敏

• 批准号: 8082092
• 负责人: RUSSELL WAYNE BROWN
• 金额: $ 1.16万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8082092
• 关键词: Acute; Adult; Affect; Affinity; Agonist; Amphetamines; Anhedonia; Animals; Antipsychotic Agents; Area; Behavior; Brain; Cell Nucleus; Chronic; Control Animal; Corpus striatum structure; Data; Development; Disease; Dopamine; Dopamine D2 Receptor; Drug abuse; General Population; Incidence; Individual; Injection of therapeutic agent; Investigation; Laboratories; Language; Lead; Microdialysis; Modeling; Names; Neonatal; Neostriatum; Nicotine; Nucleus Accumbens; Pathway interactions; Pharmaceutical Preparations; Play; Population; Positive Reinforcements; Principal Investigator; Psychological reinforcement; Quinpirole; Rattus; Research; Rodent Model; Role; Saline; Schizophrenia; Sex Characteristics; Speed; Substance abuse problem; Symptoms; System; Time; Woman; base; bean; behavioral sensitization; design; drug of abuse; drug reinforcement; neonate; neurochemistry; programs; psychostimulant; relating to nervous system; research study; stimulant abuse

DESCRIPTION (provided by applicant): This proposal is designed to analyze the effects of amphetamine sensitization on dopamine release in the nucleus accumbens in a rodent model of schizophrenia. Research has shown that substance abuse in the schizophrenic population is approximately 2-5 times higher than that of the general public. The abuse of drug in the psychostimulants class, such as amphetamine and nicotine, are the most frequently abused drugs in the schizophrenic population. There is not a definitive explanation as to why there is a high level of drug abuse in this population, as substance abuse in schizophrenia has not been a well-investigated issue. Although there is typically higher overall functioning in women schizophrenics, this disappears with substance abuse, and women are more vulnerable to the negative effects of psychostimulant abuse. The rodent model of schizophrenia utilized in this proposal is based on long-term priming of the dopamine D2 receptor through neonatal administration of quinpirole, a dopamine D2/D3 agonist. Past research has demonstrated that neonatal quinpirole administration produces priming of the dopamine D2 receptor throughout the animal's lifetime. Preliminary data of this proposal demonstrates that an acute injection of amphetamine to D2-primed rats produced a 4-fold increase in dopamine microdialysate in the neostriatum compared to animals non-D2-primed rats neonatally treated with saline. The increase in dopamine release induced by amphetamine may be important in explaining the increased incidence of psychostimulant abuse in the schizophrenic population, and may lead to reduction in anhedonia, a negative symptom of the disorder. The proposal is designed to analyze three specific aims: 1) Compare the effects of amphetamine sensitization and analyze amphetamine's effects on dopamine release in the nucleus accumbens core utilizing microdialysis in D2-receptor-primed versus non-D2-receptor primed rats; 2) Investigate the role of dopamine D1 and D2 receptors in sensitization and dopamine release in the nucleus accumbens core in D2- versus non-D2-primed rats; 3) Analyze sex differences in amphetamine-induced behavioral sensitization and its relationship to dopamine microdialysis in the NAcc in D2- versus non-D2-primed rats. Plain language description: Schizophrenia affects approximately 1% of the U.S. population, and this population is 2-5 times more likely to use or abuse stimulants than the general public. This proposal is designed to investigate the effects of chronic amphetamine (street name: Speed) administration on behavior and neurochemistry of rats that been given a drug manipulation during development that mimics the neurochemistry of schizophrenia.

描述（由申请人提供）：该提案旨在分析苯丙胺致敏对精神分裂症啮齿动物模型中多巴胺释放的影响。研究表明，精神分裂症人口中的药物滥用大约是公众的2-5倍。精神分裂剂和尼古丁等精神刺激剂中的药物滥用是精神分裂症人群中最常滥用的药物。关于为什么在这个人群中滥用毒品的原因没有明确的解释，因为精神分裂症的滥用毒品并不是一个充分的问题。尽管女性精神分裂症患者的总体功能通常较高，但由于滥用毒品而消失，而女性更容易受到精神刺激滥用的负面影响。该提案中使用的精神分裂症的啮齿动物模型是基于多巴胺D2受体的长期启动，通过新生儿给药（奎尼螺旋罗）（多巴胺D2/D3激动剂）。过去的研究表明，在整个动物的一生中，新生儿奎因螺菌的给药会产生多巴胺D2受体的启动。该提案的初步数据表明，与非D2-培训的大鼠相比，新纹状体中的多巴胺微透析剂急性注射到D2-priment的大鼠的多巴胺微透析剂增加了4倍。苯丙胺引起的多巴胺释放的增加对于解释精神分裂症人群的精神刺激滥用的发生率可能很重要，并且可能导致Anhedonia的减少，这是该疾病的负面症状。该提案旨在分析三个特定目的：1）比较苯丙胺致敏的影响，并分析了使用D2-受体培训中的微透析的伏隔核中苯丙胺对多巴胺释放的影响； 2）研究多巴胺D1和D2受体在D2-与非d2-primed大鼠中伏隔核中敏化和多巴胺释放中的作用； 3）分析苯丙胺诱导的行为敏感性的性别差异及其与D2-与非D2-primed大鼠的NACC中NACC中多巴胺微透析的关系。简单的语言描述：精神分裂症影响了美国人群的大约1％，使用或滥用兴奋剂的可能性是公众的2-5倍。该建议旨在研究慢性苯丙胺（街道名称：速度）给药对大鼠的行为和神经化学的影响，这些行为和神经化学在发育过程中进行了药物操纵，以模仿精神分裂症的神经化学。