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

• Published in: European journal of pharmacology Vol. 323; no. 2-3; pp. R5 - R7
• Main Authors: TU ANH PHAN, GRAY, A. M, NYCE, J. W
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 04.04.1997
• Subjects: Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Ethanol - blood; Ethanol - pharmacology; Male; Medical sciences; Mice; Motor Activity - drug effects; Oligonucleotides, Antisense - pharmacology; Receptors, Purinergic P1 - genetics; Receptors, Purinergic P1 - metabolism; Toxicology; Nervous system diseases; Targeting; Ethanol; Rat; Toxicity; Motor system disorder; Rodentia; Central nervous system; A1 Adenosine receptor; Corpus striatum; Antisense oligonucleotide; Biological activity; Vertebrata; Chemotherapy; Sensorimotor coordination; Biological fixation; Experimental disease; Mammalia; Treatment; Animal; Central nervous system disease; Intracerebral administration; Neurological disorder
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)00147-7

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 (Bmax = 0.350 +/- 0.07, Kd = 1.87 +/- 0.50 nM). No effect upon striatal adenosine A2 receptor content was observed (Bmax = 0.415 +/- 0.04, Kd = 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 (Bmax = 0.666 +/- 0.11, Kd = 1.32 +/- 0.27 nM) or adenosine A2 receptor content (Bmax = 0.501 +/- 0.08; Kd = 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.