DRUG REINFORCEMENT PROCESSES--NEUROHUMORS AND BRAIN LOCI

来自临床和行为药理学的证据表明 过度使用维生素C会导致疾病。 发生的过程 当一个刺激是根据导致 这种行为的增加被称为强化。 的 这些过程的神经生物学基质一直在研究中 25年来，在一些领域取得了重大进展， 地区 该研究项目建议使用最近开发的 鉴定和进一步表征神经体液的方法， 启动和调节强化过程的大脑位点。 这将是 通过允许大鼠颅内自我施用神经体液来实现 （神经递质，神经调质，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 确定潜在的内在增强性能。 间歇 强化和双杠杆判别程序的时间表将被 用于区分自我管理的强化效果 引起反应的特性。 衰减 通过神经递质受体拮抗剂的自我给药将 证明了负责这种效应的受体的特异性。 辣根过氧化物酶和（3 H）-脯氨酸-（3 H）-亮氨酸逆行和 顺行运输将识别神经元投射到 或来自自我给药部位的神经元的投射区域。 这些 神经元通路，可能介导的强化性能， 神经体液将以神经毒素损伤为特征， 将受体拮抗剂颅内输注到这些确定的区域 并评估这些治疗对自身给药的影响。 颅内自我给药神经体液与药物的相关性 强化过程将通过允许动物选择 静脉注射可卡因和颅内神经体液 自我管理。 这些实验将增加对 大脑行为的相互作用，并可能使代理的发展， 更具体地调节这些系统中的活性，和/或 提出了治疗成瘾性疾病的新方法。

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.