Central nervous system effects of acetate: contribution to the central effects of ethanol.
Acetate, resulting from ethanol metabolism in the liver, is released into the circulation and is utilized in a number of tissues, including the brain. In its metabolism, acetate leads to the production of adenosine, a powerful physiological mediator. We have investigated the effect of acetate on central nervous system (CNS) function in rodents. Sodium acetate in doses resulting in blood concentrations comparable to those attained after the administration of 1 to 2 g/kg ethanol, had significant CNS effects. Both ethanol and acetate produced a dose-dependent impairment of motor coordination. This effect of acetate was fully blocked by the adenosine receptor blocker 8-phenyltheophylline (8PT), whereas the dose-response relationship for ethanol was shifted to the right by about 30%. The inspired concentration of sevoflurane to achieve anesthesia was significantly reduced by both these agents. General anesthesia was potentiated in a dose-dependent fashion by ethanol and by acetate. The effect of acetate on anesthetic requirements was fully blocked by 8PT. The effect of ethanol on sevoflurane anesthetic requirements was inhibited by 22 to 35% by 8PT. Locomotor activity in mice was reduced by acetate in a dose-dependent fashion, an effect that was also fully blocked by 8PT. On the other hand, ethanol at a dose of 1 to 2 g/kg increased locomotor activity. This likely results from a direct stimulatory effect of ethanol, opposed by an inhibitor effect of acetate. The administration of 8PT enhanced the stimulation of locomotor activity induced by ethanol. In conclusion, acetate, a product of ethanol metabolism has significant CNS effects that can either potentiate or antagonize the effects of the ethanol molecule per se.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Toronto, Ontario, Canada.
F J
FJ
Carmichael
Y
Y
Israel
M
M
Crawford
K
K
Minhas
V
V
Saldivia
S
S
Sandrin
P
P
Campisi
H
H
Orrego
D000085:Acetates / Q000097:blood / Q000494:pharmacology*; D019342:Acetic Acid; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000085:Acetates; D000431:Ethanol; D013806:Theophylline; C028322:8-phenyltheophylline; D019342:Acetic Acid