BEHAVIORAL SENSITIZATION

这个项目的总体目标是研究现象学和 行为学的生化和神经解剖学基础 敏化。该模型被用来研究行为的演化。 病理学以及条件反射或语境依赖在这一过程中的作用 行为。环境和药物干预措施包括 调查的目的是试图改变敏感化的过程 发展与表达。到目前为止的重要发现包括 演示如下：1)新的两天可卡因敏化 完全受条件限制或依赖于上下文的范式；2)第二 敏化范式，使用为期三天的训练方案， 产生比上述更持久的条件性敏感化 范式；3)完整的多巴胺功能对 发展，但不表达上下文相关的敏感化；4) 杏仁核和伏隔核在两天条件反射中的作用 敏化；5)可卡因与NMDA的交叉敏化 拮抗剂MK-801，以及可卡因和普鲁卡因(一种局部麻醉剂)之间的作用 这是由灵长类动物自己给药的)，但不是在可卡因和 利多卡因(非自行给药)或可卡因和咖啡因； 阻断MK-801，锂， 尼莫地平、可乐定和安定，但不使用卡马西平、丙谷胺 (CCK拮抗剂)，或α-螺旋CRF(CRF拮抗剂)；7)阻断 可乐定、安定和可乐定的条件性致敏作用的表达 尼莫地平。

The overall objectives of this project are to study the phenomenology and the biochemical and neuroanatomical substrates of behavioral sensitization. This model is used to study the evolution of behavioral pathology and the role of conditioning or context-dependency in such behaviors. Environmental and pharmacological interventions are investigated in an attempt to alter the course of sensitization development and expression. Significant findings to date include demonstration of the following: 1) a novel-two day cocaine sensitization paradigm which is entirely conditioned or context-dependent; 2) a second sensitization paradigm, using a three-day training regimen, which produces longer-lasting conditioned sensitization than the above paradigm; 3) the requirement of intact dopamine function for the development, but not expression of context-dependent sensitization; 4) a role for the amygdala and nucleus accumbens in the two-day conditioned sensitization; 5) cross-sensitization between cocaine and the NMDA antagonist MK-801, and between cocaine and procaine (a local anesthetic that is self-administered by primates), but not between cocaine and lidocaine (which is not self-administered) or cocaine and caffeine; 6) blockade of the development of sensitization by MK-801, lithium, nimodipine, clonidine and diazepam, but not by carbamazepine, proglumide (CCK antagonist), or alpha-helical CRF (CRF antagonist); 7) blockade of the expression of conditioned sensitization by clonidine, diazepam, and nimodipine.