Neurotrophins and Cocaine-Induced Neuronal Plasticity

描述(由申请人提供)： 反复接触可卡因会导致大鼠运动和刻板行为的渐进性和持久性增强，这一现象被称为行为敏感化。行为敏感化背后的神经元可塑性导致可卡因的刺激动机效应增强。因此，对行为敏化机制的研究可以为中枢神经系统的可塑性提供新的见解，这可能有助于阐明人类精神刺激性成瘾者转向强迫药物使用的机制，并有助于开发针对这些疾病的新的药物治疗方法。神经营养素-3(NT-3)和脑源性神经营养因子(BDNF)与可卡因诱导的行为敏感化的启动和表达有关。这项拨款申请的目的是1)评估急性和重复注射可卡因对新纹状体、伏隔核核心和外壳中NT-3和BDNF表达的影响；以及II)评估反义寡核苷酸抑制新纹状体、伏隔核核心和外壳中TrkB和TrkC受体表达对可卡因诱导的行为敏化的影响。

DESCRIPTION (provided by applicant): Repeated exposure to cocaine leads to a progressive and enduring augmentation of locomotor and stereotyped behaviors in rats, a phenomenon known as behavioral sensitization. The neuronal plasticity underlying behavioral sensitization results in the enhancement of the incentive motivational effects of cocaine. Thus, studies examining the mechanisms underlying behavioral sensitization could provide new insight into plasticity in the CNS that may help elucidate the mechanisms underlying the shift to compulsive drug use among human psychostimulant addicts and lead to the development of novel pharmacological treatments for these diseases. Neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF) have been linked to the initiation and expression of cocaine-induced behavioral sensitization. The goal of this grant application is 1) to assess the influence of acute and repeated injections of cocaine on the expression of NT-3 and BDNF in the neostriatum, core and shell of the nucleus accumbens; and ii) to assess the effect of antisense oligonucleotide suppression of TrkB and TrkC receptor expression in the neostriatum, core or shell of the nucleus accumbens on cocaine-induced behavioral sensitization.