EFFECT OF 5,7-DIHYDROXYTRYPTAMINE ON AUDIOGENIC-SEIZURES IN GENETICALLY EPILEPSY-PRONE RATS

To further assess the role of 5-HT in the modulation of audiogenic sei zures (AGS) in the Genetically Epilepsy-Prone Rat (GEPR), changes in A GS severity after widespread chronic depletion of brain 5-HT by intrac erebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT) were examined in moderate seizure GEPRs (GEPR-3s). Following treatment with 5,7-DHT (150 mu g/30 mu l), a significant increase in seizure se verity was observed at 2, 3 and 4 weeks as compared to vehicle-injecte d controls. The increase in seizure severity was evidenced by a signif icant increase in the incidence of tonic convulsions in 5,7-DHT treate d animals (53% in treated animals compared to 0% in vehicle treated co ntrols) over the testing period. Interestingly, the latency to wild ru nning was increased in 5,7-DHT treated GEPRs, suggesting that depletio n of brain 5-HT may slow initiation of AGS. Neurochemical analysis rev ealed marked depletion of 5-HT in the cortex (-96%), hippocampus (-94% ), thalamus (-80%), hypothalamus (-62%), midbrain (-51%) and pons-medu lla (-52%) in animals that received 5,7-DHT. However, no significant r eductions in brain norepinephrine content were observed in any of the regions assayed due to the pretreatment of all animals with protriptyl ine. The present findings lend further support for an inhibitory actio n of brain 5-HT on audiogenic seizures in GEPRs.