Evaluating models of cocaine self-administration

评估可卡因自我给药模型

• 批准号: 7483732
• 负责人: LORI A KNACKSTEDT
• 金额: $ 2.44万
• 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: 2006-09-15 至 2008-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7483732
• 关键词: Affect; Animal Model; Animals; Behavioral; Biological Markers; Cocaine; Cues; DLG4 gene; Daily; Data; Dopamine; Dose; Drug Addiction; Drug Controls; Exhibits; Figs - dietary; Glutamates; Goals; Homer protein; Hour; Human; Immunoblotting; Injection of therapeutic agent; Length; Measures; Microdialysis; Modeling; Molecular; Monitor; Nucleus Accumbens; Pharmaceutical Preparations; Proteins; Publications; Rattus; Saline; Self Administration; Self-Administered; System; Time; Training; Week; Withdrawal; addiction; cupidin; dopamine system; drug relapse; experience; neuroadaptation; neurochemistry; presynaptic density protein 95; research study; response; transmission process

DESCRIPTION (provided by applicant): The specific aims of the proposed experiments are to examine the potential differences between rats allowed extended access (6 hours) to cocaine self-administration and rats given the traditional short access (1 hour); in 1) locomotor sensitization, 2) cocaine- and cue-induced reinstatement of cocaine-seeking after withdrawal, 3) the differences in basal and stimulated glutamate and dopamine levels, 4) molecular changes that accompany cocaine self-administration, namely in glutamate transmission-related proteins such as AGS3, PSD-95, mGluR1/5, xCT, GluR1, GluR2/3, and the Homer proteins. Rats trained to self-administer cocaine will experience two weeks of withdrawal and will then be challenged with three doses of cocaine (3, 10, and 30 mg/kg IP) to examine both locomotor sensitization and the ability of cues and cocaine to elicit the reinstatement of cocaine-seeking. Two weeks after the last self-administration session, the basal levels of glutamate and the stimulated levels of glutamate and dopamine in the nucleus accumbens will be measured via microdialysis. At the same time point that these behavioral and neurochemical changes will be monitored, we will also look for changes in known molecular markers of addiction via immunoblots.

描述（由申请人提供）：拟议实验的具体目的是检查大鼠之间的潜在差异允许扩展接入（6小时）到可卡因自我给药和大鼠鉴于传统的短距离通道（1小时）；在1）运动敏化时，2）可卡因和提示引起的戒断后恢复可卡因的寻求可卡因，3）3）基底和刺激的谷氨酸和多巴胺水平的差异，4）4）分子变化，这些变化是可卡因伴随可卡因自我添加的自我admmentation，即glutamate-ags-ags-ags-ags-ags-ags-ags-pegs-pegs-peg-psd-psd-psd-psd-psd-psd-psd-psd-psd-psd-psd-5 XCT，Glur1，Glur2/3和Homer蛋白。接受过自动加可卡因训练的大鼠将经历两周的戒断，然后将受到三剂可卡因（3、10和30 mg/kg IP）的挑战，以检查运动运动的敏感性以及提示和可卡因的能力，以引起Cocaine-seeking的重新启动。在上次自我管理会话后两周，伏隔核中谷氨酸和谷氨酸和多巴胺的刺激水平将通过微透析进行测量。在将监测这些行为和神经化学变化的同时，我们还将通过免疫印迹来寻找已知的成瘾分子标志物的变化。