Cortico-striatal BDNF and cocaine withdrawal and relapse

皮质纹状体 BDNF 和可卡因戒断和复发

• 批准号: 7055563
• 负责人: WILLIAM J BERGLIND
• 金额: $ 3.37万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055563
• 关键词: behavior test; behavioral /social science research tag; brain derived neurotrophic factor; cocaine; drug withdrawal; enzyme linked immunosorbent assay; gene expression; growth factor receptors; laboratory rat; mitogen activated protein kinase; neural transmission; phospholipase C; phosphorylation; predoctoral investigator; prefrontal lobe /cortex; psychopharmacology; reinforcer; relapse /recurrence

DESCRIPTION (provided by applicant): Chronic cocaine induces long-lasting neuro-adaptations within the mesocorticolimbic reward pathways (the motivational circuit) that are thought to underlie the manifestation of addictive behaviors. Recently, brain-derived neurotrophic factor (BDNF), within the NAcc and the ventral tegmental area (VTA), has emerged as a modulator of cocaine reward and reinstatement (Grimm et al. 2003; Hall et al. 2003; Horger et al, 1999; Lu et al. 2004). The cortico-striatal pathway from the prefrontal cortex (PFC) to the NAcc is critical in the manifestation of relapse behavior (Kalivas 2004; McFarland et al. 2003), and less is known about the role of BDNF neuro-transmission in this pathway following chronic cocaine. In the present study we will first examine BDNF protein expression within the motivational circuit following withdrawal from cocaine self-administration. Secondly, we will manipulate PFC neurotransmission by infusing BDNF directly into the PFC. We will then evaluate the enduring effects of intra-PFC BDNF infusions on reinstatement testing, TrkB receptor cell surface expression, and the phosphorylation state of the TrkB receptor, ERK, AKT, and PLCg, in the motivational circuit.

描述（由申请人提供）： 慢性可卡因会在中皮质边缘奖赏通路（动机回路）内诱导持久的神经适应，这被认为是成瘾行为表现的基础。最近，NAcc 和腹侧被盖区 (VTA) 内的脑源性神经营养因子 (BDNF) 已成为可卡因奖赏和恢复的调节剂（Grimm 等人，2003 年；Hall 等人，2003 年；Horger 等人， 1999；卢等。从前额皮质 (PFC) 到 NAcc 的皮质-纹状体通路对于复发行为的表现至关重要（Kalivas 2004；McFarland 等人 2003），而关于 BDNF 神经传递在该通路中的作用知之甚少。慢性可卡因。在本研究中，我们将首先检查戒断可卡因自我给药后动机回路中 BDNF 蛋白的表达。其次，我们将通过将 BDNF 直接注入 PFC 来操纵 PFC 神经传递。然后，我们将评估 PFC 内 BDNF 输注对激励回路中恢复测试、TrkB 受体细胞表面表达以及 TrkB 受体、ERK、AKT 和 PLCg 的磷酸化状态的持久影响。