Disinhibition reduces extracellular glutamine and elevates extracellular glutamate in rat hippocampus in vivo

摘要

Disinhibition was induced in the hippocampal CA1/CA3 region of normal adult rats by unilateral perfusion of the GABA(A)R antagonist, 4-[6-imino-3-(4-methoxyphenyl)pyridazinl-yl] butanoic acid hydrobromide (gabazine), or a GABA(B)R antagonist, p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid (CGP 35348), through a microdialysis probe. Effects of disinhibition on EEG recordings and the concentrations of extracellular glutamate (GLU(ECF)), the major excitatory neurotransmitter, and of extracellular glutamine (GLN(ECF)), its precursor, were examined bilaterally in freely behaving rats. Unilateral perfusion of 10 mu M gabazine in artificial CSF of normal electrolyte composition for 34 min induced epileptiform discharges which represent synchronized glutamatergic population bursts, not only in the gabazine-perfused ipsilateral hippocampus, but also in the aCSF-perfused contralateral hippocampus. The concentration of GLU(ECF) remained unchanged, but the concentration of its precursor, GLN(ECF), decreased to 73 +/- 14% (n=5) of the baseline during frequent epileptiform discharges, not only in the ipsilateral, but also in the contralateral hippocampus, where the change can be attributed to recurrent epileptiform discharges per se, with recovery to 95% of baseline when epileptiform discharges diminished.