LASTING INCREASE IN SEROTONIN 5-HT1A BUT NOT 5-HT4 RECEPTOR SUBTYPES IN THE KINDLED RAT DENTATE GYRUS - DISSOCIATION FROM LOCAL PRESYNAPTICEFFECTS

We examined the effect of kindling on serotonergic neurotransmission i n the hippocampus by measuring serotonin (5-HT) release and uptake in hippocampal synaptosomes and 5-HT1A and 5-HT4 receptor subtypes during and at different times after electrical kindling of the dentate gyrus . Using quantitative receptor autoradiography, we found that binding o f 8-[H-3]hydroxy-2-(di-n-propylamino) tetralin ([H-3]8-OH-DPAT) to 5-H T1A receptors was selectively increased by 20% on average (p < 0.05) i n the dentate gyrus of the stimulated and contralateral hippocampus 2 days after stage 2 (stereotypes and occasional retraction of a forelim b) and by 100% on average (p < 0.05) 1 week after stage 5 (tonic-cloni c seizures) compared with sham-stimulated rats. A 20% increase (p < 0. 05) was observed 1 month after the last generalized seizure. No change s were found after a single afterdischarge. 5-HT4 receptors, which col ocalize with 5-HT1A receptors on hippocampal neurons, were not modifie d in kindled tissue, [H-3]5-HT uptake and its release as well as the 5 -HT1B autoreceptor function did not differ from shams in hippocampal s ynaptosomes at stages 2 and 5, Systemic administration of 100 and 1,00 0 mu g kg(-1) 8-OH-DPAT or 1,000 mu g kg(-1) WAY-100,635, 30 min befor e each electrical stimulation, did not significantly alter kindling pr ogression or the occurrence of stage 5 seizures in fully kindled rats. The changes in 5-HT1A receptor density in the dentate gyrus are part of the plastic modifications occurring during kindling and may contrib ute to modulating tissue hyperexcitability.