DRUG REINFORCEMENT PROCESSES--NEUROHUMORS AND BRAIN LOCI

来自临床和行为药理学的证据表明会上瘾 失调症是指过度使用强化剂。发生的过程 当刺激的交付取决于导致 这种行为的增加被称为加固。这个 这些过程的神经生物学底物一直在研究中。 25年来，在一些领域取得了重大进展 区域。这项研究项目提出了使用最近开发的 鉴定和进一步表征神经体液和 启动和调节强化过程的大脑基因座。这将是 通过允许大鼠脑内自我给药神经体液来实现的 (神经递质、神经调节剂、神经激素)直接转化为离散的 这些内源性配体通常被释放到的大脑区域 确定潜在的内在增强性能。间歇性 加强和两级区别对待程序的时间表如下 用于辨证自拟补肾药的补益作用 反应产生的神经体液具有诱人的特性。衰减 神经递质受体拮抗剂的自我给药将 证明负责这一效应的受体的特异性。 辣根过氧化物酶和(~3H)-脯氨酸-(~3H)-亮氨酸逆行 顺行运输将识别投射到 或自我给药部位神经元的投射区域。这些 神经通路潜在地介导了血管紧张素转换酶 神经体液的特征是神经毒素损伤或 将受体拮抗剂颅内注入这些已识别的区域 并评估这些治疗对自我给药的影响。 脑内自我给药神经体液与药物的相关性 加固过程将通过允许动物选择 静脉注射可卡因或颅内神经体液之间 自治。这些实验将增加对 大脑-行为相互作用，并可能使代理的发展 更具体地说，可能和/或调节这些系统中的活动 为成瘾障碍提供新的治疗方法。

Evidence from clinical and behavioral pharmacology suggest addictive disorders to be the excessive use of reinforcers. The processes that occur when a stimulus is delivered contingent on behavior that results in increases in that behavior is referred to as reinforcement. The neurobiological substrates of these processes have been under investigation for two and one-half decades, resulting in significant progress in some areas. This research project proposes the use of recently developed methodologies to identify and further characterize the neurohumors and brain loci that initiate and mediate reinforcement processes. This will be accomplished by allowing rats to intracranially self-administer neurohumors (neurotransmitters, neuromodulators, neurohormones) directly into discrete brain regions where these endogenous ligands are normally released to determine potential intrinsic reinforcing properties. Intermittent schedules of reinforcement and two-lever discrimination procedures will be used to differentiate the reinforcing effects of self-administered neurohumors from response eliciting properties. Attenuation of self-administration by neurotransmitter receptor antagonists will demonstrate the specificity of the receptors responsible for this effect. Horseradish peroxidase and (3H)-proline-(3H)-leucine retrograde and anterograde transport will identify cell bodies for neurons projecting to or projection areas from neurons at the self-administration site. These neuronal pathways that potentially mediate the reinforcing properties of the neurohumor will be characterized with neurotoxin lesions or intracranial infusion of receptor antagonists into these identified areas and the effects of these treatments assessed on the self-administration. The relevance of the intracranially self-administered neurohumor to drug reinforcement processes will be determined by allowing animals to choose between intravenous cocaine or intracranial neurohumor self-administration. These experiments will increase understanding of brain-behavior interactions and could make the development of agents to more specifically modulate activity in these systems possible and/or suggest new therapeutic approaches to addictive disorders.