Brain adenosinergic modulation of acute ethanol-induced motor impairment.
A striking similarity in the pharmacology of ethanol and adenosine provided circumstantial evidence for possible modulation by brain adenosine of the CNS effects of ethanol. We were first to report that ethanol-induced motor impairment is modulated by brain adenosine. Further studies showed that ethanol-induced motor impairment is modulated by adenosine centrally rather by a peripheral hemodynamic change, in part, because icv-injected [3H]R-PIA did not escape into peripheral circulation. Within the cerebellum ethanol-induced motor impairment is functionally related to an increase in the maximum number of adenosine receptors, an inhibition of adenosine uptake, an increase in adenosine release and, in an adenosine-sensitive manner, with a decrease in glutamate release. Although A2 receptor affinity and A2/A1 affinity ratio correlate better with the ED50 of adenosine agonists to accentuate ethanol-induced motor impairment, the high affinity cerebellar A1 receptors appear equally important, in part, because R-PIA vs S-PIA showed 40-fold greater potency in accentuating ethanol-induced motor impairment. Recent data from this laboratory point toward the presence of specific adenosinergic sites in the cerebellum which modulate ethanol-induced motor impairment through adenosine A1 receptors, the latter appear coupled via Gi protein to AC-cAMP system. These data further support our hypothesis that brain adenosine modulates ethanol-induced motor impairment.
Dar
M S
MS
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D000431:Ethanol / Q000633:toxicity*; D018698:Glutamic Acid / Q000502:physiology; D051379:Mice; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000145:classification / Q000187:drug effects / Q000502:physiology
D018047:Receptors, Purinergic P1; D000431:Ethanol; D018698:Glutamic Acid; D000241:Adenosine