Acute restraint-mediated increases in glutamate levels in the rat brain: an in vivo ¹H-MRS study at 4.7 T.

It is well known that a variety of stressors induces a significant alteration in various putative neurotransmitters in the mammalian CNS. However, relatively little attention has been paid on the alteration of central glutamate neurotransmission, which is a major excitatory neurotransmitter in the brain. The present study aimed to determine whether acute restraint stress induces the changes in neurotransmitter level, especially glutamate, in rat brain and to examine whether 1-h recovery time after the termination of stress can revert to its pre-stress state. In vivo ¹H-NMR spectra were acquired from the cerebral cortex and hippocampus (control: N = 10, stress: N = 10, stress + 1 h rest: N = 10) immediately or after 1 h rest from restraint stress. All in vivo proton spectra were automatically analyzed using LCModel. We found that acute restraint stress induced significant increase in glutamate concentrations in the cerebral cortex and the hippocampus of rat. However, the level could not revert to its pre-stress state by the end of 1-h recovery period in cerebral cortex of rats. In addition, glutamine/glutamate ratio, which may function as an index of the glutamatergic neurotransmission, was significantly lower in the cerebral cortex of both stress and 1 h stress + 1 h recovery groups, as compared to control. Our finding may provide important evidence for altered glutamatergic activity after the stress and suggest a potential biochemical marker for eventual diagnosis and/or therapy monitoring in mood disorder.