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 ac etyl-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 mu g). Acute treatment with acetyl-L-carnitine was found to increase the behavioral deficit after sodium cyanide, these f indings were replicated in a second experiment. Based on these results it c an be argued that an acute administration of acetyl-L-carnitine appears to potentiate a sodium cyanide-induced behavioral deficit. An additional in vi tro experiment with rat brain synaptosomes showed clear effects of administ ered 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 depletio n. The negative behavioral findings are in contrast with our previously fou nd protective effect of chronic treatment with acetyl-L-carnitine (via drin king water) on the sodium cyanide-induced behavioral deficit. Since chronic acetyl-L-carnitine treatment has no effect on the phosphoinositide metabol ism it was suggested that acetyl-L-carnitine may act via the formation of a n 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 d iscrepancy in behavioral results between the chronic vs acute treatment of acetyl-L-carnitine at present. Further research is needed to characterize t he mechanism of action of acetyl-L-carnitine in relation to sodium cyanide. (C) 1998 Elsevier Science Ltd. All rights reserved.