Murakami Gen, Nakamura Masato, Takita Masatoshi, Ishida Yasushi, Ueki Takatoshi, Nakahara Daiichiro
Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Cognition and Action Research Group, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Neuropsychopharmacology. 2015 Nov;40(12):2686-95. doi: 10.1038/npp.2015.115. Epub 2015 Apr 29.
Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1 min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats.
越来越多的证据表明，前额叶胶质细胞对细胞外谷氨酸（GLU）的调节在厌恶行为中起着关键作用。然而，关于前额叶胶质细胞是否在奖赏行为中调节GLU水平，目前尚无定论。为了解决这个问题，我们测量了与奖赏行为相关的大鼠内侧前额叶皮质（PFC）中的GLU外流。我们采用内侧前脑束（MFB）的颅内自我刺激（ICSS）作为奖赏行为。使用微透析结合在线荧光检测由GLU脱氢酶催化的GLU与NAD(+)反应产生的NADH来间接测量GLU，时间分辨率为1分钟。ICSS导致内侧PFC中细胞外GLU每分钟都发生变化，刺激期间略有下降，随后上升。这种双向变化对河豚毒素不敏感，并被胶质毒素氟柠檬酸消除。为了证实并扩展先前关于厌恶诱导内侧PFC中细胞外GLU增加的研究，我们还测量了与厌恶刺激（固定应激）相关的前额叶GLU外流。这种应激引起的细胞外GLU的时间变化与ICSS期间观察到的明显不同。在厌恶刺激期间检测到GLU迅速增加，随后大幅增加。这种双峰变化对河豚毒素不敏感，与ICSS检测到的相似。这些发现表明，前额叶胶质细胞对与大鼠ICSS行为相关的细胞外GLU进行双向调节，并揭示内侧PFC中GLU神经化学的胶质调节有助于大鼠的奖赏行为和厌恶行为。
