Effect of norepinephrine release on adrenoceptors in severe seizure genetically epilepsy-prone rats

The genetically epilepsy-prone rat (GEPR) seizure model is characterized by extensive abnormalities in brain noradrenergic function. Earlier studies h ad suggested that GEPRs might not regulate adrenoceptors in a normal fashio n. The purpose of the present study was to determine if GEPR-9s are capable of up and down regulation of alpha(1)- and beta-adrenoceptors in response to increments or decrements in extracellular norepinephrine. Seizure induct ion has been shown to increase extracellular norepinephrine. Chronic sound or electroshock induced seizures caused down regulation of P-adrenoceptors in frontal cortex and in hippocampus from GEPR-9s. Similarly, chronic daily treatment with the norepinephrine reuptake inhibitor desmethylimipramine p roduced down regulation of P-adrenoceptors in frontal cortex and in hippoca mpus from GEPR-9s. As is the case in neurologically normal animals, chronic electroshock-induced seizure did not cause down regulation of P-adrenocept ors in 6-hydroxydopamine pretreated GEPR-9s. Chronic electroshock treatment also caused up-regulation of alpha(1)-adrenoceptors in frontal cortex but not in hippocampus. In 6-hydroxydopamine pretreated GEPR-9s, chronic electr oshock treatment caused a further up-regulation of alpha(1)-adrenoceptors i n frontal cortex but not in hippocampus. Taken together, these results indi cate that GEPR-9s are capable of up and down regulation of alpha(1)- and be ta-adrenoceptors in a manner that is qualitatively similar to the regulatio n of these receptors in normal animals. Whether the regulation of brain adr enoceptors is quantitatively different in GEPRs from normal animals remains to be established. (C) 2000 Elsevier Science B.V. All rights reserved.