Acute effects of acetyl-L-carnitine on sodium cyanide-induced behavioral and biochemical deficits.
In the present study we investigated the effects of acute treatment with acetyl-L-carnitine (50 mg/kg, i.v. 90 min before the sodium cyanide injection) on a sodium cyanide-induced behavioral deficit in the Morris water escape task. In a first experiment the spatial discrimination performance of the rats was found to be dose-dependently impaired after an i.c.v. injection of sodium cyanide (2.5 and 5.0 microg). Acute treatment with acetyl-L-carnitine was found to increase the behavioral deficit after sodium cyanide. These findings were replicated in a second experiment. Based on these results it can be argued that an acute administration of acetyl-L-carnitine appears to potentiate a sodium cyanide-induced behavioral deficit. An additional in vitro experiment with rat brain synaptosomes showed clear effects of administered sodium cyanide on the energy-dependent incorporation of inositol into phosphoinositides and on the ATP concentration. In vitro acetyl-L-carnitine administration had no effect on the sodium cyanide-induced energy depletion. The negative behavioral findings are in contrast with our previously found protective effect of chronic treatment with acetyl-L-carnitine (via drinking water) on the sodium cyanide-induced behavioral deficit. Since chronic acetyl-L-carnitine treatment has no effect on the phosphoinositide metabolism it was suggested that acetyl-L-carnitine may act via the formation of an ATP-independent reservoir of activated acyl groups. Thus, fatty acids as acylated derivatives can be used for reacylation processes during an acute period of energy depletion. However, we have no clear explanation for the discrepancy in behavioral results between the chronic vs acute treatment of acetyl-L-carnitine at present. Further research is needed to characterize the mechanism of action of acetyl-L-carnitine in relation to sodium cyanide.
Prickaerts
J
J
Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience EURON, Maastricht University, The Netherlands. jos.prickaerts@np.unimaas.nl
Blokland
A
A
Bothmer
J
J
Honig
W
W
Markerink-Van Ittersum
M
M
Jolles
J
J
D000108:Acetylcarnitine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012966:Sodium Cyanide / Q000633:toxicity*
D010716:Phosphatidylinositols; D000108:Acetylcarnitine; D000255:Adenosine Triphosphate; D012966:Sodium Cyanide