ADENOSINE A2 RECEPTORS AND PSYCHOSTIMULANT INTERACTIONS

腺苷 A2 受体和精神兴奋剂的相互作用

• 批准号: 2517911
• 负责人: MICHAEL A SCHWARZSCHILD
• 金额: $ 27.44万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517911
• 关键词: adenosine; amphetamines; behavioral habituation /sensitization; corpus striatum; dopamine receptor; drug addiction antagonist; drug administration rate /duration; drug interactions; gel mobility shift assay; immunocytochemistry; in situ hybridization; laboratory rat; limbic system; messenger RNA; neural plasticity; neurochemistry; neurons; neuropharmacology; nucleoproteins; prosencephalon; psychotropic drugs; purinergic receptor; receptor expression; transcription factor; western blottings

DESCRIPTION: (Applicant's Abstract) Long-term administration of psychostimulant drugs produces enduring changes in behavior. It is likely that the long-term changes in brain function associated with prolonged drug exposure are important to addictive behavior. The molecular mechanisms underlying the persistent alteration in brain function associated with prolonged psychostimulant exposure are poorly understood. The behavioral effects of the psychostimulant amphetamine are dependent on activation of dopamine receptors within the striatum and limbic forebrain. Repeated administration of psychostimulants to rodents produces alterations in nuclear proteins which may underlie long-lasting changes in behavior. The A2a subtype of adenosine receptor is expressed in and regulates responsiveness of D2-expressing striatal and limbic forebrain neurons, and modulates the behavioral and nuclear responses of acute amphetamine. The A1 adenosine receptor also modulates AMPH-induced behavior, but the anatomical basis of this A1 effect is not understood. We hypothesize that striatal and limbic forebrain A2a and A1 adenosine receptors are sites where the acute effects of AMPH and enduring changes in brain function following chronic AMPH can be regulated. The expression of striatal and limbic forebrain A2a and A1 receptors will be characterized and the roles that these adenosinergic receptors play in modulating the behavioral and nuclear effects of acute and chronic AMPH administration will be investigated. These experiments will begin to identify nuclear mechanisms underlying this form of drug-induced neural plasticity which are vulnerable to modulation by forebrain adenosinergic receptors.

描述：（申请人摘要） 长期服用精神兴奋剂药物会产生持久的 行为上的改变 很可能大脑的长期变化 与长期药物暴露相关的功能对成瘾性很重要 行为 持续改变的分子机制 与长期精神兴奋剂接触相关的脑功能很差， 明白 精神兴奋剂安非他明的行为效应是 依赖于纹状体和边缘系统内多巴胺受体的激活 前脑 对啮齿类动物反复使用精神兴奋剂会产生 核蛋白的改变可能是长期变化的基础， 行为 腺苷受体的A2a亚型表达于 调节D2表达的纹状体和边缘前脑的反应性 神经元，并调节行为和核反应的急性 安非他明 A1腺苷受体也调节AMPH诱导的 行为，但这种A1效应的解剖学基础尚不清楚。 我们 假设纹状体和边缘前脑A2a和A1腺苷 受体是AMPH的急性作用和持久变化的部位， 慢性AMPH后的脑功能可被调节。 的表达 将表征纹状体和边缘前脑A2 a和A1受体， 这些腺苷能受体在调节 急性和慢性AMPH给药的行为和核效应将 追究 这些实验将开始， 这种形式的药物诱导的神经可塑性的潜在机制， 易受前脑腺苷能受体的调节。