Electrophysiology of Behavioral Sensitization

描述（由申请人提供）：多巴胺能投射至核 大脑皮层和前额叶皮层与 到吸毒在重复施用精神兴奋剂（即，可卡因， d-安非他明，甲基安非他明），动物通常表现出增加的行为 当给予激发刺激剂剂量时激活;这种现象已经被 被称为“行为敏感化”，它与增加的 成瘾受试者在重复摄入药物时表现出的反应，特别是 戒断后对毒品的渴望我们的计划是探索大脑区域 参与建立和表达这种敏感性， 电生理技术。目前关于引起 和表达敏感性是建立在几个独立的研究基础上的。的 例如，行为敏感化的表达涉及激活 多巴胺投射到脑桥核另一方面 前额叶皮层到腹侧被盖的脑电投射 区域（多巴胺投射到丘脑的细胞群 来源），以引起敏感性。我们一直在研究 前额叶皮层、中脑核和腹侧核的相互作用 从生理学的角度来看，这些地区表现出相互 控制他们的信息处理的相互作用;因此，我们 假设这种相互作用在致敏动物中会改变。 同时记录这些神经元的电活动是一种最佳的方法。 解决这种相互作用在诱导和/或 行为敏感化的表达。体内细胞内记录将 用于评估甲基苯丙胺重复给药后的变化。 甲基苯丙胺被选为致敏剂，因为其最近的增长， 在美国被滥用的药物

DESCRIPTION (provided by applicant): The dopaminergic projection to the nucleus accumbens and prefrontal cortex has been implicated in the mechanisms leading to drug abuse. Upon repeated administration of psychostimulants (i.e., cocaine, d-amphetamine, methamphetamine), animals typically exhibit increased behavioral activation when given a challenge stimulant dose; this phenomenon has been termed "behavioral sensitization" and it has been related to the increased responses addicted subjects exhibit upon repeated drug intake, particularly to the craving for drug upon withdrawal. Our plan is to explore the brain regions involved in the establishment and expression of such sensitization using electrophysiological techniques. The current views on the mechanisms evoking and expressing sensitization have been built upon several separate studies. The expression of behavioral sensitization, for example, involves the activation of dopamine projections to the nucleus accumbens. On the other hand, the glutamatergic projection from the prefrontal cortex to the ventral tegmental area (the group of cells from which the dopamine projection to the accumbens originates) is required to elicit sensitization. We have been studying the interactions among the prefrontal cortex, nucleus accumbens and ventral tegmental area from a physiological perspective. These regions exhibit mutual interactions that control their information processing; therefore, we hypothesize that such interactions would be altered in sensitized animals. Recording the electrical activity of these neurons simultaneously is an optimal means to address the role of such interactions in the induction and/or expression of behavioral sensitization. In vivo intracellular recordings will be employed to assess changes upon repeated administration of methamphetamine. Methamphetamine was chosen as the sensitizing agent given its recent growth as an abused substance in the U.S.