Central adenosinergic system involvement in ethanol-induced motor incoordination in mice.
To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as enprofylline on ethanol-(i.p.)-induced motor incoordination was evaluated by rotorod. Adenosine agonists and antagonists dose dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i.p. Enprofylline, a weak adenosine antagonist but potent inhibitor of cyclic AMP phosphodiesterase, did not alter ethanol's motor incoordination, further supporting involvement of brain adenosine receptor mechanism(s) in ethanol-adenosine interactions. Results from R-PIA and N6-(S-phenylisopropyl)adenosine experiments showed nearly a 40-fold greater potency of R-vs. S-diastereoisomer, suggesting predominance of adenosine A1 subtype. However, 5'-(N-cyclopropyl)-carboxamidoadenosine data indicate complexity of the mechanism(s) and point toward an additional involvement of a yet unknown subtype of adenosine A2. No effect of ethanol on blood or brain levels of [3H]R-PIA was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol. There was no escape of i.c.v.-administered [3H]R-PIA from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol-adenosine interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Dar
M S
MS
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina.
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001259:Ataxia / Q000139:chemically induced*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000502:physiology; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium; D014970:Xanthines / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011983:Receptors, Purinergic; D014970:Xanthines; D014316:Tritium; D010660:Phenylisopropyladenosine; D000431:Ethanol; C024311:N-cyclopropyl adenosine-5'-carboxamide; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; C034347:enprofylline; D000241:Adenosine