Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.
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.
Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Gen
G
Murakami
Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Masato
M
Nakamura
Cognition and Action Research Group, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Masatoshi
M
Takita
Department of Psychiatry, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Yasushi
Y
Ishida
Department of Anatomy and Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.|Department of Biofunctional Imaging, Medical Photonics Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takatoshi
T
Ueki
Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Department of Biofunctional Imaging, Medical Photonics Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Daiichiro
D
Nakahara
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D002951:Citrates / Q000494:pharmacology; D003216:Conditioning, Operant; D004797:Enzyme-Linked Immunosorbent Assay; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology*; D017551:Microdialysis; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012653:Self Stimulation; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D002951:Citrates; D026941:Sodium Channel Blockers; C007744:fluorocitrate; D018698:Glutamic Acid; D013779:Tetrodotoxin