ABNORMALITIES IN 5-HT1A AND 5-HT1B RECEPTOR-BINDING IN SEVERE-SEIZUREGENETICALLY EPILEPSY-PRONE RATS (GEPR-9S)

The present study was designed to determine whether abnormalities in s erotonin receptor binding co-exist with the presynaptic serotonergic d eficits that have previously been identified in the genetically epilep sy-prone rat (GEPR) brain. In vitro binding of [H-3]8-OH-DPAT (0.16-10 .3 nM) to 5-HT1A receptor sites was found to be decreased in the hippo campus of severe seizure GEPRs (GEPR-9s) when compared to nonepileptic control rats, while no difference in [H-3]8-OH-DPAT binding was obser ved in the GEPR-9 corpora quadrigemina or midbrain tegmentum. The decr eased binding of [H-3]8-OH-DPAT to hippocampal membranes was due to a decrease in B-max (P < 0.001), rather than to a change in the K-d Conv ersely, in vitro binding of [I-125]cyanopindolol (2-400 pM) to 5-HT1B receptor sites was increased in the GEPR-9 hippocampus, corpora quadri gemina and midbrain tegmentum when compared to nonepileptic control ra ts. The increased binding of [I-125]cyanopindolol in all three regions resulted from an increase in the B-max (P < 0.05), rather than a chan ge in the K-d. These findings suggest that in addition to the innate r eduction in 5-HT presynaptic markers, GEPR-9s also exhibit abnormaliti es in the density of 5-HT1A and 5-HT1B receptors in some regions of th e brain. Inasmuch as serotonin acts to attenuate audiogenic seizures i n GEPRs, these abnormalities in 5-HT receptor binding may contribute t o the seizure susceptibility exhibited by these animals.