Incubation of cocaine-craving relates to glutamate over-flow within ventromedial prefrontal cortex.
Incubation of cocaine-craving relates to glutamate over-flow within ventromedial prefrontal cortex.
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DOI：
10.1016/j.neuropharm.2015.10.038
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发表时间：
2016-03
影响因子：
4.7
通讯作者：
Szumlinski KK
中科院分区：
文献类型：
--
作者：
Shin CB;Serchia MM;Shahin JR;Ruppert-Majer MA;Kippin TE;Szumlinski KK
由药物相关线索引发的渴望在长期戒毒中会加剧--这种现象被称为“渴望的潜伏期”--而人类成瘾者的药物渴望与额叶皮质过度活跃有关。在这里，我们采用了大鼠模型的线索引起的可卡因渴望来测试的假设，即时间依赖性的潜伏期的线索引起的可卡因渴望与适应多巴胺和谷氨酸神经传递的腹内侧前额叶皮层（vmPFC）。训练大鼠自我静脉注射可卡因（6小时/天× 10天），并在停药3天或30天后，在2小时试验期间进行体内微透析程序，以检测线索诱导的可卡因渴望。对照组大鼠接受训练，以自我给予蔗糖颗粒或不接受初级维生素。可卡因寻求大鼠表现出戒断依赖性的增加和减少，分别在线索引起的谷氨酸和多巴胺的释放。这些模式的神经化学变化没有观察到在任何控制条件。因此，vmPFC谷氨酸末端的线索超敏性是一种生化相关的孵育可卡因渴望，可能源于多巴胺在这一地区的失调。
Craving elicited by drug-associated cues intensifies across protracted drug abstinence – a phenomenon termed “incubation of craving” – and drug-craving in human addicts correlates with frontal cortical hyperactivity. Herein, we employed a rat model of cue-elicited cocaine-craving to test the hypothesis that the time-dependent incubation of cue-elicited cocaine-craving is associated with adaptations in dopamine and glutamate neurotransmission within the ventromedial prefrontal cortex (vmPFC). Rats were trained to self-administer intravenous cocaine (6h/day × 10 days) and underwent in vivo microdialysis procedures during 2h-tests for cue-elicited cocaine-craving at either 3 or 30 days withdrawal. Controls rats were trained to either self-administer sucrose pellets or received no primary reinforcer. Cocaine-seeking rats exhibited a withdrawal-dependent increase and decrease, respectively, in cue-elicited glutamate and dopamine release. These patterns of neurochemical change were not observed in either control condition. Thus, cue-hypersensitivity of vmPFC glutamate terminals is a biochemical correlate of incubated cocaine-craving that may stem from dopamine dysregulation in this region.