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首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Repeated cocaine enhances ventral hippocampal-stimulated dopamine efflux in the nucleus accumbens and alters ventral hippocampal NMDA receptor subunit expression
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Repeated cocaine enhances ventral hippocampal-stimulated dopamine efflux in the nucleus accumbens and alters ventral hippocampal NMDA receptor subunit expression

机译：重复可卡因增强伏隔核中腹侧海马刺激的多巴胺流出并改变腹侧海马NMDA受体亚基表达

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摘要

Dopaminergic neurotransmission in the nucleus accumbens is important for various reward-related cognitive processes including reinforcement learning. Repeated cocaine enhances hippocampal synaptic plasticity, and phasic elevations of accumbal dopamine evoked by unconditioned stimuli are dependent on impulse flow from the ventral hippocampus. Therefore, sensitized hippocampal activity may be one mechanism by which drugs of abuse enhance limbic dopaminergic activity. In this study, in vivo microdialysis in freely moving adult male Sprague-Dawley rats was used to investigate the effect of repeated cocaine on ventral hippocampus-mediated dopaminergic transmission within the medial shell of the nucleus accumbens. Following seven daily injections of saline or cocaine (20 mg/kg, ip), unilateral infusion of N-methyl-o-aspartate (NMDA, 0.5 mu g) into the ventral hippocampus transiently increased both motoric activity and ipsilateral dopamine efflux in the medial shell of the nucleus accumbens, and this effect was greater in rats that received repeated cocaine compared to controls that received repeated saline. In addition, repeated cocaine altered NMDA receptor subunit expression in the ventral hippocampus, reducing the NR2A : NR2B subunit ratio. Together, these results suggest that repeated exposure to cocaine produces maladaptive ventral hippocampal-nucleus accumbens communication, in part through changes in glutamate receptor composition.
机译：伏伏核中的多巴胺能神经传递对于各种与奖励有关的认知过程（包括强化学习）很重要。重复的可卡因可增强海马突触可塑性，无条件刺激引起的伏隔多巴胺阶段性升高取决于腹侧海马的冲动流量。因此，致敏的海马活动可能是滥用药物增强边缘多巴胺能活动的一种机制。在这项研究中，在自由移动的成年雄性Sprague-Dawley大鼠中进行体内微透析，以研究重复可卡因对伏隔核内侧壳内腹侧海马介导的多巴胺能传递的影响。每天注射七次盐水或可卡因（20 mg / kg，腹腔注射）后，单侧将N-甲基-o-天门冬氨酸盐（NMDA，0.5μg）注入腹侧海马体中，可立即提高运动能力和同侧多巴胺流出伏隔核的壳，与重复给予盐水的对照组相比，重复给予可卡因的大鼠的这种作用更大。此外，反复的可卡因改变了腹侧海马中NMDA受体亚单位的表达，从而降低了NR2A：NR2B亚单位的比例。总之，这些结果表明，反复接触可卡因会部分通过谷氨酸受体组成的变化而产生适应不良的腹侧海马-伏隔核沟通。

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