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  • Title: Abnormalities in 5-HT1A and 5-HT1B receptor binding in severe-seizure genetically epilepsy-prone rats (GEPR-9s).
    Author: Statnick MA, Dailey JW, Jobe PC, Browning RA.
    Journal: Neuropharmacology; 1996 Jan; 35(1):111-8. PubMed ID: 8684590.
    Abstract:
    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.
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