Electrophysiology of Behavioral Sensitization

描述(申请人提供)：多巴胺能投射到核团 伏隔核和前额叶皮质被认为参与了 与吸毒有关。在反复给予精神刺激剂(即，可卡因， D-苯丙胺、甲基苯丙胺)，动物通常表现出更多的行为 当给予刺激性刺激剂剂量时激活；这种现象已经被 称为“行为敏感化”，它与增加的 成瘾受试者在反复吸食药物时表现出的反应，特别是对 戒毒后对毒品的渴望。我们的计划是探索大脑区域 参与这种敏化的建立和表达，使用 电生理技术。关于诱发机制的最新观点 和表达敏化已经建立在几个独立的研究基础上。这个 例如，行为敏化的表达涉及到激活 多巴胺投射到伏隔核。另一方面， 前额叶皮质向腹侧被盖的谷氨酸能投射 区域(多巴胺投射到伏隔核的细胞群 需要)才能引起敏感化。我们一直在研究 前额叶皮质、伏隔核和腹侧的相互作用 从生理学角度看被盖区。这些地区表现出相互的 控制其信息处理的交互；因此，我们 假设这种相互作用会在致敏动物身上发生改变。 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 表现为行为敏感化。活体细胞内记录将 被用来评估反复服用甲基苯丙胺后的变化。 甲基苯丙胺被选为致敏剂，因为它最近增长为 在美国被滥用的物质。

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.