Time course of changes in the concentrations of amino acids in the brain structures of pentylenetetrazole-kindled rats

The results showed that the development of seizures (pentylenetetrazole, PTZ-induced kindling; PTZ was administered to rats at a subconvulsive dose of 35 mg/kg three times a week, i.p.) was accompanied by a progressive recruitment of limbic structures and a characteristic pattern of changes in the brain tissue concentration of examined amino acids (ex vivo measurements, 1.5 h after the last dose of PTZ). The earliest and homogenous increase in the excitatory (glutamate and alanine) and inhibitory (GABA and taurine) amino acids was observed in the entorhinal cortex (at stages 1 and 2 according to Racine's scale), and this effect was maintained at the fifth stage of kindling (except for glutamate). At the fifth stage of kindling, glutamate was elevated in the amygdala, nucleus accumbens and piriform cortex, whereas alanine content was increased in the hippocampus, amygdala, striatum, nucleus accumbens and piriform cortex. In the case of GABA, a significant increase in the local concentration of this amino acid was found in rats with stage 1 and 2 seizures in the prefrontal and entorhinal cortices and a decrease was present in amygdala. Kindling raised the local level of taurine in the entorhinal cortex (stage 1 and 2 seizures), amygdala, nucleus accumbens and piriform cortex (stage 5 seizures). These data confirm the conclusion that separate seizure circuitries in the forebrain structures mutually interact to facilitate and/or inhibit one another. Overall, these data suggest that there is a shift in the balance between neurotransmitters toward increased production of excitatory amino acids.