EFFECT OF ACETYL-L-CARNITINE ON EXTRACELLULAR AMINO-ACID LEVELS INVIVO IN RAT-BRAIN REGIONS

Acetyl-L-carnitine (ALCAR) was found to have beneficial effects in sen ile patients. In recent years many of its effects on the nervous syste m have been examined, but its mechanism(s) of action remains to be elu cidated. We previously reported that it causes release of dopamine in the striatum. In the present paper we report that ALCAR, when administ ered at intracerebral sites via microdialysis, stimulates the release of amino acids in a concentration-dependent and regionally heterogeneo us manner. The effect was strong in the striatum and cerebellum, less so in the frontal cortex, and weak in the thalamus. Seven amino acids were measured: the increase in the level of aspartate, glutamate, and was substantial, and the increase in the level of glycine, serine, thr eonine, alanine, and glutamine in the microdialysate was minor. The st imulatory effect of ALCAR on the release of amino acids in the striatu m was inhibited by the muscarinic antagonist atropine, but was not inh ibited by the nicotinic antagonist mecamylamine. The effect of ALCAR o n the levels of most of the amino acids tested was independent of the presence of Ca2+ in the perfusate. These results indicate that ALCAR, when administered intracerebrally at fairly high concentrations, can a ffect the level and the release not only of such neurotransmitters as acetylcholine and dopamine, but also of amino acids. The mechanism of action of ALCAR on the release of cerebral amino acids may involve the participation of muscarinic receptors or may be mediated through the release of dopamine, but the lack of Ca2+ dependence indicates a relea se from the cytoplasmic amino acid pool, possibly through the effect o f ALCAR on cell membrane permeability.