Intrastriatal adenosine A 1 receptor antisense oligodeoxynucleotide blocks ethanol-induced motor incoordination

Abstract

Intrastriatal administration of a 21-mer phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A 1 receptor blocked ethanol-induced motor incoordination in the rat and reduced striatal adenosine A 1 receptor content, as judged by specific binding of the A 1-specific 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 receptor content was observed ( B max=0.415±0.04, K d=13.13±1.25 nM) with the A 2-specific ligand 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine. A mismatched control oligodeoxynucleotide of identical G-C base composition and general sequence structure was without effect 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. These results confirm an important role of the striatal adenosine A 1 receptor in mediating certain motor-related physiological effects of ethanol.