ANTICONVULSANT EFFECTS OF INTRAHIPPOCAMPAL INJECTION OF TRH IN AMYGDALA-KINDLED RATS

THE anticonvulsant effects of intra-hippocampal thyrotropin-release ho rmone (TRH) were examined in amygdala kindled rats. Subjects were impl anted unilaterally with an electrode in the amygdala and bilaterally w ith guide cannulae in the hippocampus, aimed at the dorsal and ventral dentate gyri. Rats were kindled daily with suprathreshold electrical stimulation (800 mu A, 1 ms pulse width, 100 Hz, duration 0.5 s) until seizures were reliably elicited. The afterdischarge (AD) duration, se izure duration, and seizure stage were recorded daily, and AD threshol ds were determined after kindling was completed. TRH was infused into each of the four cannulae of freely moving rats at doses of 0 (vehicle ), 1.25, 2.5 and 5 mu g/site. Five minutes after the last infusion, th e rats received electrical stimulation at their AD threshold (mean = 1 35 mu A) + 50 mu A. TRH reduced the AD and seizure duration in a dose- dependent manner. At the dose of 2.5 mu g/site, TRH also reduced AD an d seizure duration in rats stimulated with suprathreshold current (800 mu A). However, TRH had minimal effects on seizure stage irrespective of the stimulation intensity. These results suggest that the seizure- induced elevations of TRH in the hippocampus, as demonstrated in previ ous studies, may be part of an endogenous anticonvulsant compensatory mechanism and that further elevations of TRH in the hippocampus can pr oduce anticonvulsant effects mainly by reducing the AD and seizure dur ation.