INTRASTRIATAL ADENOSINE A(1) RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE BLOCKS ETHANOL-INDUCED MOTOR INCOORDINATION

Intrastriatal administration of a 21-mer phosphorothioate antisense ol igodeoxynucleotide targeting the adenosine A(1) receptor blocked ethan ol-induced motor incoordination in the rat and reduced striatal adenos ine A(1) receptor content, as judged by specific binding of the A(1)-s pecific ligand 8-cyclopentyl-1,3-dipropylxanthine (B-max = 0.350 +/- 0 .07, K-d = 1.87 +/- 0.50 nM). No effect upon striatal adenosine A(2) r eceptor content was observed (B-max = 0.415 +/- 0.04, K-d = 13.13 +/- 1.25 nM) with the A(2)-specific ligand yl)phenethylanlino-5'-N-ethylca rboxamidoadenosine. A mismatched control oligodeoxynucleotide of ident ical G-C base composition and general sequence structure was without e ffect on adenosine A(1) receptor (B-max = 0.666 +/- 0.11, K-d = 1.32 /- 0.27 nM) or adenosine A(2) receptor content (B-max = 0.501 +/- 0.08 ; K-d = 14.65 +/- 1.82 nM) or ethanol-induced motor incoordination. Th ese results confirm an important role of the striatal adenosine A(1) r eceptor in mediating certain motor-related physiological effects of et hanol.