SOMATOSTATIN RELEASE IS ENHANCED IN THE HIPPOCAMPUS OF PARTIALLY AND FULLY KINDLED RATS

The release of somatostatin (somatostatin-like immunoreactivity) from hippocampal slices during the development of hippocampal kindling in rats was measured under resting and depolarizing conditions. Preliminary experiments in naive rats showed that the spontaneous efflux of somatostatin (4.0 +/- 0.3 fmol/ml every 10 min) was independent of external Ca2+ but was reduced to 71.5 +/- 6% of baseline (P < 0.05) during 20 min incubation with 5 muM tetrodotoxin. Neuronal depolarization with 25, 50 and 100 mM KCl induced a Ca2+-dependent somatostatin release, respectively 4.3 +/- 0.4, 16.7 +/- 1.6 and 22.0 +/- 1.3 times baseline (P < 0.01). Veratridine caused a dose-dependent Ca2+ and tetrodotoxin (5 muM) sensitive release ranging from 6.5 +/- 0.1 to 13.0 +/- 1.4 times baseline at 1.4 muM and 50 muM respectively (P < 0.01). One week after the last of three consecutive stage 5 seizures (full seizure expression) or 48 h after the last stage 2 stimulation (preconvulsive stage), 50 mM KCl-induced somatostatin release was significantly higher (1.8 +/- 0.1, P < 0,01) than in shams (animals implanted with electrodes but not stimulated) in the stimulated and contralateral hippocampus. Somatostatin release measured under resting conditions was increased by 1.5 times in the stimulated hippocampus at stage 2 (P < 0.05) and by 2.2 and 1.7 times in both hippocampi at stage 5 (P < 0.01). Forty-eight hours after the induction of a single afterdischarge no significant changes were found in either spontaneous or 50 mM KCl-induced release of somatostatin. The tissue concentration of somatostatin did not vary significantly in either side of the hippocampus at stage 2 compared to shams but at stage 5 increases of 56% and 71 % respectively (P < 0.05) were found in the stimulated and contralateral hippocampus. The present results provide the first evidence of enhanced neuronal release of somatostatin during kindling which suggests that this neuropeptide may play some role in epileptogenesis.