ADENOSINE A2 RECEPTORS AND PSYCHOSTIMULANT INTERACTIONS

描述：(申请人摘要) 长期服用精神刺激性药物会产生持久的效果 行为的改变。很可能是大脑的长期变化 与长时间接触毒品有关的功能对成瘾很重要 行为。慢性阻塞性肺疾病持续改变的分子机制 与长期接触精神刺激剂相关的大脑功能较差 明白了。精神刺激剂苯丙胺的行为影响是 依赖纹状体和边缘的多巴胺受体的激活 前脑。反复给啮齿动物服用精神刺激剂会产生 核蛋白的改变，这可能是长期变化的基础 行为。腺苷受体的A2a亚型在和 调节表达D2的纹状体和边缘前脑的反应性 并调节急性脑缺血大鼠的行为和核反应。 安非他命。腺苷A1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的急性影响和持久的变化 慢性AMPH后的脑功能是可以调节的。的表达方式 纹状体和边缘前脑A2a和A1受体的特征 这些腺苷能受体在调节细胞周期中的作用 急性和慢性AMPH给药的行为和核影响将 被调查。这些实验将开始识别核子 这种药物诱导的神经可塑性的潜在机制是 易受前脑腺苷能受体的调节。

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.