No abstract

Microdialysis has been used for in vivo studies of extracellular amino acids in rat brain. We describe a method where a probe was designed to be implanted vertically. This probe is suitable for regional stereotaxic studies of the rat brain. The dialysis probe was perfused with Ringer's solution and the perfusates were analysed for their amino acid content with a high performance liquid chromatography (HPLC) technique. An orthophthaldialdehyde derivative of the amino acids was formed before the sample was injected onto the column. In vitro studies of the dialysis probe show that the relative recovery of substances outside the membrane is dependent on perfusion speed and length of dialysing membrane but not on the concentration outside. We were also able to show that the probe was within the blood-brain barrier (BBB) when implanted into the brain since after intravenous injection of Na99mTcO4, a substance that cannot pass through the intact BBB, it was not possible to recover any isotope from the perfusate. We conclude that microdialysis is a unique method of studying regional neurochemical events within the BBB, for example, changes in putative amino acid neurotransmitters and their metabolites.

The extracellular levels of aspartate, glutamate, serine, glutamine, glycine, alanine and GABA were studied in vivo with the microdialysis technique in 15 different regions of the rat brain. The effect of high K+ on the overflow of these amino acids was also studied. These results were compared with those from a regional dissection of 17 brain regions in which the tissue content of the same amino acids was determined. The in vivo data showed an unevenly distributed KCl response of aspartate, glutamate, taurine and GABA, all of which are putative neurotransmitters. It was not possible to predict the response to high K+ from the magnitude of the unstimulated overflow. Glutamine overflow was inversely related to that of glutamate during the high K+ stimulus, which is consistent with glutamine being the main precursor of glutamate. Only for GABA and alanine was overflow proportional to the tissue level in the different regions studied.

No abstract

Brain tissue levels and in vivo release of substance P (SP) and neurokinin A (NKA) and GABA were measured bilaterally in striatum and substantia nigra of the rat, after a unilateral 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Sham injected animals served as controls. The dopamine denervation decreased the tissue levels of SP in striatum (-38%) ipsilateral to the lesion and in substantia nigra both ipsi- (-54%) and contralateral (-38%) to the lesion. NKA was not significantly changed in the striatum, but decreased (like SP) in the substantia nigra both ipsi- (-50%) and contralateral (-40%) to the lesion. GABA tissue levels increased in the denervated striatum (+20%) and remained unchanged in substantia nigra at both sides. The extracellular levels of SP, NKA and GABA were measured with microdialysis in vivo at basal conditions and during stimulation with potassium administered locally via the microdialysis probe. The stimulated release of SP and NKA in the substantia nigra ipsilateral to the lesion was compared to in sham operated animals reduced with 39% and 64%, respectively, while no change in SP or NKA release was detected in the striatum. The basal release of GABA in the striatum was increased with 296% and with 76% during stimulation in the dopamine denervated striatum, while no change in GABA basal or stimulated release was detected in the substantia nigra. We suggest that the increased GABA release in the dopamine denervated striatum may be due to a decreased dopamine mediated inhibition of local GABA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)