Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 2010 Aug;211(3):267-75. doi: 10.1007/s00213-010-1890-z. Epub 2010 Jun 12.
Dopamine and glutamate in the nucleus accumbens (NAS) are differentially implicated in cocaine-directed behavior.
We sought to compare extracellular fluctuations of dopamine and glutamate in core and shell of NAS associated with operant responding during cocaine self-administration, extinction, and yoked cocaine administration.
Rats were trained to lever-press for cocaine or saline under FR1 before undergoing microdialysis testing during cocaine self-administration, extinction, or yoked cocaine administration. Microdialysis samples were collected every 20 min and were analyzed for dopamine and glutamate with high-performance liquid chromatography.
Rats actively lever-pressed during cocaine self-administration and extinction. However, lever-pressing was minimal during yoked cocaine administration in both cocaine-trained and saline-trained rats. Dopamine was elevated throughout cocaine self-administration and yoked cocaine administration. The extent of cocaine-evoked dopamine was greater in shell than in core, greater in cocaine-trained than in saline-trained rats, and greater during self-administration than during yoked administration. Dopamine was also elevated in core (first 60 min) and in shell (first 40 min) during extinction. Basal concentration of glutamate, but not dopamine, was lower in cocaine-trained than in saline-trained rats. In cocaine-trained rats, glutamate was elevated during cocaine self-administration and extinction but was depressed below baseline during yoked cocaine administration. The extent and direction of glutamate fluctuation was similar between core and shell. In saline-trained rats, glutamate was not affected by yoked cocaine.
Distinct patterns of dopamine and glutamate fluctuations in core and shell appear to underlie characteristic patterns of lever-pressing associated with cocaine self-administration, extinction, and yoked cocaine administration.
伏隔核(NAS)中的多巴胺和谷氨酸在可卡因导向行为中分别具有不同的作用。
我们试图比较可卡因自我给药、消退和偶联可卡因给药期间与操作性反应相关的 NAS 核心和壳部细胞外多巴胺和谷氨酸的波动。
在进行可卡因自我给药、消退或偶联可卡因给药的微透析测试之前,大鼠在 FR1 下接受可卡因或盐水的按压训练。每隔 20 分钟收集一次微透析样本,并使用高效液相色谱法分析多巴胺和谷氨酸。
大鼠在可卡因自我给药和消退期间积极按压杠杆。然而,在可卡因训练和盐水训练的大鼠中,偶联可卡因给药期间的按压行为很少。多巴胺在可卡因自我给药和偶联可卡因给药期间均升高。壳部可卡因诱发的多巴胺水平高于核心,可卡因训练大鼠高于盐水训练大鼠,自我给药时高于偶联给药时。在消退期间,核心(前 60 分钟)和壳部(前 40 分钟)多巴胺也升高。谷氨酸的基础浓度,而不是多巴胺,在可卡因训练大鼠中低于盐水训练大鼠。在可卡因训练大鼠中,谷氨酸在可卡因自我给药和消退期间升高,但在偶联可卡因给药期间低于基线。核心和壳部的谷氨酸波动幅度和方向相似。在盐水训练的大鼠中,偶联的可卡因对谷氨酸没有影响。
核心和壳部多巴胺和谷氨酸波动的不同模式似乎是与可卡因自我给药、消退和偶联可卡因给药相关的按压行为的特征模式的基础。