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)
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adenosine ethanol adenosine N6-(R-phenylisopropyl)adenosine R-PIA N6-(S-phenylisopropyl)adenosine 5'-(N-cyclopropyl)-carboxamidoadenosine theophylline 8-p-(sulfophenyl)theophylline enprofylline adenosine ethanol Adenosine ethanol ethanol adenosine adenosine ethanol adenosine Enprofylline adenosine N6-(S-phenylisopropyl)adenosine cyclic AMP ethanol ethanol adenosine adenosine A1 adenosine A2 adenosine receptor adenosine adenosine Adenosine adenosine adenosine adenosine adenosine adenosine cyclic AMP phosphodiesterase adenosine receptor 5'-(N-cyclopropyl)-carboxamidoadenosine adenosine [3H]R-PIA adenosine ethanol [3H]R-PIA