Abnormalities in 5-HT1A and 5-HT1B receptor binding in severe-seizure genetically epilepsy-prone rats (GEPR-9s).
The present study was designed to determine whether abnormalities in serotonin receptor binding co-exist with the presynaptic serotonergic deficits that have previously been identified in the genetically epilepsy-prone rat (GEPR) brain. In vitro binding of [3H]8-OH-DPAT (0.16-10.3 nM) to 5-HT1A receptor sites was found to be decreased in the hippocampus of severe seizure GEPRs (GEPR-9s) when compared to nonepileptic control rats, while no difference in [3H]8-OH-DPAT binding was observed in the GEPR-9 corpora quadrigemina or midbrain tegmentum. The decreased binding of [3H]8-OH-DPAT to hippocampal membranes was due to a decrease in Bmax (P < 0.001), rather than to a change in the Kd. Conversely, in vitro binding of [125I]cyanopindolol (2-400 pM) to 5-HT1B receptor sites was increased in the GEPR-9 hippocampus, corpora quadrigemina and midbrain tegmentum when compared to nonepileptic control rats. The increased binding of [125I]cyanopindolol in all three regions resulted from an increase in the Bmax (P < 0.05), rather than a change in the Kd. These finding suggest that in addition to the innate reduction in 5-HT presynaptic markers, GEPR-9s also exhibit abnormalities in the density of 5-HT1A and 5-HT1B receptors in some regions of the brain. Inasmuch as serotonin acts to attenuate audiogenic seizures in GEPRs, these abnormalities in 5-HT receptor binding may contribute to the seizure susceptibility exhibited by these animals.
Statnick
M A
MA
Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901, USA.
Dailey
J W
JW
Jobe
P C
PC
Browning
R A
RA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C047975:cyanopindolol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol