Behavioural and biochemical effects of acute central metabolic inhibition: effects of acetyl-l-carnitine.
In the present study we evaluated a new method to assess the behavioural and biochemical effects of a brief period of acute hypoxia in the brain. In this method, cyanide is injected into the lateral ventricles. Spatial navigation performance in a Morris task was found to be impaired 1 and 5 min after an i.c.v. injection of 5.0 micrograms cyanide but not after 2.5 micrograms cyanide. Increased rate of phosphatidic acid formation, reflecting increased phospholipase C activity, were observed after injection of 5.0 micrograms cyanide, indicating that energy-dependent phosphoinositide metabolism was affected. Chronic treatment with acetyl-l-carnitine attenuated the cyanide-induced behavioural deficit, but had no effect on energy-dependent phosphoinositide metabolism. The results suggest that, in this model, acetyl-l-carnitine may act via free fatty acid metabolism, by increasing the reservoir of activated acyl groups which are involved in the reacylation of membrane phospholipids.
Department of Neuropsychology and Psychobiology, University of Limburg, Maastricht, Netherlands.
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A
Blokland
J
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Bothmer
W
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Honig
J
J
Jolles
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002855:Chromatography, Thin Layer; D003486:Cyanides / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D004193:Discrimination Learning / Q000187:drug effects; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions
D003486:Cyanides; D004075:Diglycerides; D010716:Phosphatidylinositols; D000108:Acetylcarnitine