An in vivo procedure for the selective inactivation of rat brain cerebral cortical α-adrenoceptors using N-ethoxycarbonyl-2-ethoxy1,2-dihydroquinoline (EEDQ)

Abstract

Intraperitoneal administration of 0.8 mg/kg N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinole (EEDQ) to rats significantly reduced α-adrenoceptor binding in cerebral cortical membranes without affecting β-adrenoceptor sites. A selective reduction in α 1-adrenoceptors was achieved by injecting yohimbine prior to EEDQ, whereas prazosin pretreatment yielded a selective reduction in α 2-adrenoceptor binding. Administration of EEDQ decreased norepinephrine-stimulated phosphate and cyclic adenosine monophosphate (cAMP) accumulation in cerebral cortical tissue as well as the cAMP response to isoproterenol in combination with 6-fluoronorepinephrine without modifying the second messenger response to isoproterenol alone. The results suggest that, under the proper conditions, EEDQ administration can selectively diminish rat brain α-adrenoceptor number and function, yielding a procedure that may be useful for defining the behavioral and physiological properties of these sites.