Intrastriatal adenosine A₁ receptor antisense oligodeoxynucleotide blocks ethanol-induced motor incoordination

Abstract

Intrastriatal administration of a 21-mer phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A₁ receptor blocked ethanol-induced motor incoordination in the rat and reduced striatal adenosine A₁ receptor content, as judged by specific binding of the A₁-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 A₂ receptor content was observed (B_max=0.415±0.04, K_d=13.13±1.25 nM) with the A₂-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 A₁ receptor (B_max=0.666±0.11, K_d=1.32±0.27 nM) or adenosine A₂ 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 A₁ receptor in mediating certain motor-related physiological effects of ethanol.