A Comparative Study of Excitatory and Inhibitory Amino Acids in Three Different Brainstem Nuclei

Abstract

This study was designed to shed more light onto the three different brainstem regions which are implicated in the pain pathway for the level of various excitatory and inhibitory neurotransmitters before and following neuronal stimulation. The in vivo microdialysis technique was used in awake, freely moving adult Sprague-Dawley rats. The neurotransmitters studied included aspartate, glutamate, GABA, glycine, and taurine. The three brainstem regions examined included the mid-brain periaqueductal gray (PAG), the medullary nucleus raphe magnus (NRM), and the spinal trigeminal nucleus (STN). Neuronal stimulation was achieved following the administration of the sodium channel activator veratridine. The highest baseline levels of glutamate (P < 0.0001), aspartate (P < 0.0001), GABA (P < 0.01), taurine (P < 0.0001), and glycine (P < 0.001) were seen in the NRM. On the other hand, the lowest baseline levels of glutamate, GABA, glycine, and taurine were found in the PAG, while that of aspartate was found in the STN. Following the administration of veratridine, the highest release of the above neurotransmitters except for the aspartate and glycine was found in the PAG where the level of glutamate increased by 1,310 +/- 293% (P < 0.001), taurine by 1,008 +/- 143% (P < 0.01), and GABA by 10,358 +/- 1,920% (P < 0.0001) when comparison was performed among the three brainstem regions and in relation to the baseline levels. The highest release of aspartate was seen in the STN (2,357 +/- 1,060%, P < 0.001), while no significant difference was associated with glycine. On the other hand, the lowest release of GABA and taurine was found in the STN (696 +/- 91 and 305 +/- 25%, respectively), and glutamate and aspartate in the NRM (558 +/- 200 and 874 +/- 315%, respectively). Our results indicate, and for the first time, that although some differences are seen in the baseline levels of the above neurotransmitters in the three regions studied, there are quite striking variations in the level of release of these neurotransmitters following neuronal stimulation in these regions. In our opinion this is the first study to describe the pain activation/modulation related changes of the excitatory and inhibitory amino acids profile of the three different brainstem areas.

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors

“…2 and 3). This observation is consistent with previous findings from other laboratories that baseline concentration of glutamate is much higher than that of GABA in the vlPAG and other brain stem region of rats (39). We recognize that it may be more difficult to detect small changes in the very large concentrations of glutamate that are normally present in the vlPAG.…”

“…More than 10 neurotransmitters or modulators, including both glutamate and GABA, have been identified in the different subdivisions of PAG (9,38,39), although there is no information regarding glutamate and GABA release in the vlPAG during somatic afferent stimulation and/or during EA.…”

“…In addition, investigators have reported that glutamate concentration in the dorsal lateral PAG increases during stimulation of muscle afferents (31). Increases in glutamate and GABA concentrations have been discovered in the PAG following chemical stimulation of the PAG neurons, although, again, the particular subdivisions were not identified (39). In addition, immunocytochemical studies have documented that ϳ40% of terminals distributed in the four subdivisions of the PAG, including the vlPAG, are GABAergic (7).…”

Release of Endogenous Amino Acids from the Hippocampus and Brain Stem from Developing and Adult Mice in Ischemia

“…depolarization-evoked release of both GABA and taurine from slices is an increase in their extracellular levels in vivo. In the mature brain stem the changes in the extracellular levels of GABA and taurine have also been similar to those evoked by veratridine, a specific depolarizing agent for neurons [30].…”

“…The extracellular taurine levels in vivo generally exceed those of aspartate, glutamate and GABA, varying from 10 to 25 lM, depending on the brain area, including the hippocampus and brain stem [10,[27][28][29]. Only the levels of glutamate in some brain stem nuclei have recently been reported to be comparable to those of taurine [30]. The extracellular concentrations of the amino acids studied are related to their total tissue concentrations.…”