Neuropeptide Levels after Pentylenetetrazol Kindling in the Rat

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Abstract
Levels of several neuropeptides were measured in the frontal cortex, dorsal hippocampus, striatum, and amygdala/pyriform cortex in rats kindled for 5 weeks by daily injection of pentylenetetrazol (30 mg/kg, i.p.). Significantly increased concentrations (by 30–140%) were found in all examined brain areas for neuropeptide Y, somatostatin (except hippocampus) and neurokinin-like immunoreactivity 10 days after the last kindling session. Similar but less pronounced changes were also found 24 h after the last seizure. The increase in total neurokinin-like immunoreactivity was due to a marked increase in neurokinin B as revealed by HPLC analysis. Increases in peptide levels, however, were restricted to fully kindled animals. At the same time no changes in levels of substance P, vasoactive intestinal polypeptide and calcitonin gene-regulated peptide were observed. Cholecystokinin octapeptide was enhanced only in the hippocampus (by 46%). The increases in neuropeptide Y, somatostatin, and neurokinin-like immunoreactivity subsided after 3 months. A markedly decreased seizure threshold was observed 10 days and 2 months after the final kindling session. No nerve cell degeneration was observed in kindled rats 24 h or 10 days after the last pentylenetetrazol injection. Some animals (2 of 4), however, exhibited signs of blood-brain barrier damage when examined 24 h after the last kindling session which may reflect the preceding convulsions. No such changes were detected after 10 days. The increases in peptide levels may suggest increased activity of respective neurons which, at least to some degree, may be associated with γ-aminobutyric acid. The changes in peptide levels may be more closely related to the kindling procedure itself than to the decreased seizure threshold of the animals.