Yuri Kiselevski, Nicholas Oganesian, Sergey Zimatkin, Andrzej Szutowicz, Stefan Angielski, Pavel Niezabitowski, Wojciech Uracz, Ryszard Gryglewski
Med Sci Monit 2003; 9(5): BR178-182
Background: The aim of this study was to estimate the role of acetate-induced metabolic changes in brain mechanisms of resistance to the narcotic effect of ethanol.
Material/Methods: Wistar rats were treated daily with ethanol (3.5 g/kg i.p. for 7 days). During alcohol treatment, the duration of ethanol-induced sleep was decreased. Levels of acetate, acetyl-CoA, adenosine, and the pool of AMP+ADP, and the activity of acetyl-CoA synthetase and 5’-nucleotidase in the brain were measured. Synaptosomal adenosine and acetylcholine release were measured
in the presence of acetate, adenosine and 2-chloroadenosine.
Results: The concentration of acetate was higher in all investigated brain regions of ethanol rats in comparison to controls. The activity of acetyl-CoA synthetase and 5’-nucleotidase, as well as the levels of adenosine and the pool of AMP+ADP were raised in cerebral cortex of ethanol rats. The synaptosomal level of adenosine was higher in control rats. Acetate causet a 3-fold increase of extrasynaptosomal adenosine level. Synaptosomes from ethanol rats showed higher
rates of Ca-dependent releases of acetylcholine. 2-chloradenosine resulted in inhibition of synaptic acetylcholine release only in control rats.
Conclusions: Ethanol causes an increase of acetate in brain and adenosine level in cerebral cortex. Acetate causes an increase of the extrasynaptic adenosine level. Prolonged ethanol treatment results in
an increase of synaptic Ca-dependent acetylcholine release. Seven-day treatment with ethanol eliminates the inhibitory effect of 2-chloroadenosine – A1 adenosine receptor agonist on synaptic Ca-dependent acetylcholine release.
Keywords: Acetic Acid - metabolism, Acetyl Coenzyme A - metabolism, Acetylcholine - metabolism, Adaptation, Physiological, Adenosine - metabolism, Animals, Brain - drug effects, Brain - metabolism, Cerebral Cortex - drug effects, Cerebral Cortex - metabolism, Ethanol - pharmacology, Male, Rats, Rats, Wistar, Sleep - drug effects, Synaptosomes - drug effects, Synaptosomes - metabolism