In vitro autoradiographic evidence for adenosine modulation of ethanol-induced motor disturbances in rats.
It was previously shown that adenosine agonists and antagonists potentiate and decrease ethanol-induced motor disturbances, respectively. This interaction of adenosine and ethanol was functionally correlated with a significant increase in Bmax of cerebellar cortical high affinity adenosine A1 receptors after a single ethanol injection. Quantitative autoradiographic analysis of adenosine A1 and A2 binding sites in rat brain was carried out in animals treated acutely with saline or ethanol. Adenosine agonist binding at A1 receptors was increased in the molecular layer of cerebellum 15 min after ethanol injection. This increase returned to control values by 60 min. Adenosine antagonist binding at A1 receptors was not altered by ethanol treatment. Inclusion of a poorly hydrolyzable analogue of GTP in the incubation medium decreased binding throughout the brain for adenosine agonists but had less effect on agonist binding in the cerebellum and hippocampus of ethanol-treated rats 15 min after injection. The inhibitory effect of the GTP analogue was equal in saline- and ethanol-treated rats after 60 min. These findings suggest that acute ethanol treatment elicits a transitory increase in adenosine A1 receptor binding that is limited to the cerebellum and hippocampus and that this increased binding reflects an increased (or stabilized) coupling of the receptors to GTP-binding proteins. Acute ethanol treatment did not alter agonist binding at the high affinity A2a subtype of adenosine receptors in striatum.
Clark
M
M
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
Dar
M S
MS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000378:metabolism*; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014316:Tritium
D010627:Phenethylamines; D011983:Receptors, Purinergic; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010660:Phenylisopropyladenosine; D006165:Guanylyl Imidodiphosphate; D000431:Ethanol; D000241:Adenosine