INTRACEREBROVENTRICULAR ADMINISTRATION OF AT(1) RECEPTOR ANTISENSE OLIGONUCLEOTIDES INHIBITS THE BEHAVIORAL ACTIONS OF ANGIOTENSIN-II

Antisense oligonucleotides were developed to study the expression and function of angiotensin type 1 (AT(1)) receptors in cultured cells and brain. In both liver epithelial WB and neuroblastoma N1E-115 cells AT (1) antisense oligomers substantially decreased AT(1) receptor density , whereas angiotensin type 2 (AT(2)) receptors remained unchanged. Sim ilarly, repeated intracerebroventricular injections of AT(1) antisense oligomers in rats decreased AT(1) receptor density in hypothalamic-th alamic-septal tissue, and AT(2) receptors were unaffected. Intracerebr oventricular antisense oligomers also attenuated drinking elicited by intracerebroventricular angiotensin II but not the cholinomimetic carb achol. Collectively, these results demonstrate that antisense oligonuc leotides attenuate angiotensin receptor expression and function in beh aving animals.