Decrease in locus coeruleus [3H]idazoxan binding site density in genetically epilepsy-prone (GEPR) rats.

Abstract

Deficits in norepinephrine synthesis, transmitter level, turnover and reuptake have been reported in the brain of genetically epilepsy-prone (GEPR) rats. We investigated the hypothesis that these alterations may trigger a compensatory downregulation of locus coeruleus alpha 2-adrenergic receptors and an upregulation of postsynaptic alpha 2-adrenergic receptor density in forebrain regions of GEPR rat brain. alpha 2-adrenergic receptor density was measured in the locus coeruleus and 7 forebrain regions of control and GEPR rats by in vitro [3H]idazoxan autoradiography. Specific [3H]idazoxan binding site density was decreased significantly in the locus coeruleus of both GEPR-3 and GEPR-9 rats compared to controls. No significant differences in specific [3H]idazoxan binding were observed in the 7 forebrain regions of GEPR-9 rats compared to control. Reduced locus coeruleus alpha 2-adrenergic receptor density in GEPR rats may produce a net increase in locus coeruleus noradrenergic cell firing, an effect which could, in part, offset the impact of reduced noradrenergic influence in GEPR rat forebrain. Additionally, decreased norepinephrine levels in GEPR rat brain may be a long-term consequence of reduced alpha 2-adrenergic receptor-mediated inhibition of locus coeruleus firing activity.