Role of adenosine A1 and A2A receptors in the alcohol withdrawal syndrome.
The role of adenosine receptor-mediated signaling was examined in the alcohol withdrawal syndrome. CD-1 mice received a liquid diet containing ethanol (6.7%, v/v) or a control liquid diet that were abruptly discontinued after 14 days of treatment. Mice consuming ethanol showed a progressive increase in signs of intoxication throughout the drinking period. Following abrupt discontinuation of ethanol diet, mice demonstrated reversible signs of handling-induced hyperexcitability that were maximal between 5-8 h. Withdrawing mice received treatment with adenosine receptor agonists at the onset of peak withdrawal (5.5 h) and withdrawal signs were blindly rated (during withdrawal hours 6 and 7). Adenosine A1-receptor agonist R-N6(phenylisopropyl)adenosine (0.15 and 0.3 mg/ kg) reduced withdrawal signs 0.5 and 1.5 h after drug administration in a dose-dependent fashion. Adenosine A2A-selective agonist 2-p-(2-carboxyethyl)phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (0.3 mg/kg) reduced withdrawal signs at both time points. In ethanol-withdrawing mice, there were significant decreases in adenosine transporter sites in striatum without changes in cortex or cerebellum. In ethanol-withdrawing mice, there were no changes in adenosine A1 and A2A receptor concentrations in cortex, striatum, or cerebellum. There appears to be a role for adenosine A1 and A2A receptors in the treatment of the ethanol withdrawal syndrome. Published by Elsevier Science Inc.
Kaplan
G B
GB
Veterans Affairs Medical Center, Providence, RI 02908, USA. gary_kaplan@brown.edu
Bharmal
N H
NH
Leite-Morris
K A
KA
Adams
W R
WR
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D010627:Phenethylamines / Q000627:therapeutic use*; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000378:metabolism
D002492:Central Nervous System Depressants; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C047235:N-(1-methyl-2-phenylethyl)adenosine; D000431:Ethanol; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine