BEHAVIORAL PHARMACOLOGY OF OPIATE-LIKE NEUROPEPTIDES

越来越多的证据表明，内源性阿片系统(EOS)可能起作用 在调节应激行为反应中的重要作用 情况。然而，进一步的进展是有限的，部分原因是 不充分或不完全的行为特征的各种阿片类药物和 压力治疗。此外，这些影响的比较将是 如果进行行为特征描述，将大大方便 在相似的实验条件下。我们的行为系统一直是 专门设计用于持续和并发监控 广泛的行为反应，包括各种衡量标准 唤醒、环境相互作用和进食行为。建议数 研究代表了旨在评估的研究的系统进展 EOS在与以下各项相关的行为组件中的角色 不同类型、不同程度的压力。急性和慢性行为 推定的MU(吗啡，美沙酮)，kappa-(酮环唑可卡因， 乙基环唑)、西格玛-((+NANM，PCP)和Delta- (D-丙氨酸-甲基-脑啡肽)阿片受体激动剂 以RAC为特征的相对纯净的阿片类拮抗剂 纳洛酮、纳曲酮和丁丙诺啡。在相同的实验下 条件、约束、噪音和接触小说的影响 环境将被确定。激烈的互动和 阿片类药物和应激效应之间的交叉耐受/敏化将是 检查以确定由以下因素引起的类似行为的程度 这些治疗是由共同的潜在机制介导的。 应激-阿片类药物的相互作用也将通过使用我们的 多室室和行为模式监测器，并带有惊吓 和社交互动范式。我们还将进一步评估这些措施的影响 去甲肾上腺素背束损毁对典型阿片类药物和 压力治疗。除了传统的压力源之外， 急性和慢性反应中所谓的应激成分中的Eos 苯丙胺和自发性精神分裂症的表观易感性 高血压大鼠对应激反应也将进行检测。细致入微的尖锐和 外源性阿片类药物和阿片类药物的慢性行为特征 各种应激源应加强我们对EOS在 对压力反应的调节。潜在的临床价值 越来越多的证据表明，压力可能会 与多种主要疾病的发病机制密切相关 精神病理学包括抑郁症和精神分裂症。此外, 对压力的反应可能与个体差异有关 确定滥用药物的倾向。

Converging evidence suggests that endogenons opioid systems (EOS) may play an important role in modulating behavioral responsiveness to stressful situations. However, further progress is limited, in part, because of inadequate or incomplete behavioral characterization of various opioid and stress treatments. In addition, comparison of these effects would be greatly facilitated if the behavioral characterization was carried out under similar experimental conditions. Our behavioral system has been specifically designed for the continuous and concurrent monitoring of a broad spectrum of behavioral responses including various measures of arousal, environmental interaction, and ingestive behaviors. The proposed research represents a systematic progression of studies designed to assess the role of EOS in the various behavioral components associated with different types and degress of stress. The acute and chronic behavioral profiles of putative mu (morphine, methadone), kappa- (ketocyclazocine, ethylcyclazocine), sigma- ((+NANM, PCP), and delta- (D-Ala2-Met5-enkephalinamide) opiate receptor agonists will be characterized in the RACs as will the relatively pure opiate antagonists naloxone, naltrexone, and diprenorphine. Under identical experimental conditions, the effects of restraint, noise, and exposure to a novel environment will be determined. Acute interactions and cross-tolerance/sensitization between opioid and stress effects will be examined to determine the extent to which similar behaviors induced by these treatments are mediated by common underlying mechanisms. Stress-opioid interactions will also be examined with the use of our multicompartment chamber and behavioral pattern monitor, and with startle and social interaction paradigms. We will also assess further the effects of NE dorsal bundle lesions on the response to representative opioid and stress treatments. In addition to the conventional stressors, the role of EOS in the alleged stress component of the acute and chronic response to amphetamine and in the apparent susceptibility of spontaneously hypertensive rats to stress will also be examined. The detailed acute and chronic behavioral characterization of exogenously administered opioids and various stressors should enhance our understanding of the role of EOS in the regulation of responsiveness to stress. The potential clinical value of this research is indicated by the accumulating evidence that stress may be significantly implicated in the pathogenesis of major forms of psychopathology including depression and schizophrenia. In addition, individual differences in responsiveness to stress may be involved in determining predisposition to drug abuse.