Effects of acetyl-L-carnitine on regional cerebral glucose metabolism in awake rats.
The time-course and relation to dose of regional metabolic rates for glucose (rCMRglc) were measured in awake adult Fischer-344 rats after administration of acetyl-L-carnitine (ALCAR), an agent that modulates neuronal energy processes and neurotransmitter synthesis. rCMRglc were determined with the quantitative [(14)C]2-deoxy-D-glucose technique in 50 brain regions at 10, 30 and 60 min after i.v. administration of ALCAR 500 mg/kg and at 30 min after ALCAR 250 and 700 mg/kg or coadministration of acetate (500 mg/kg) and carnitine (500 mg/kg). ALCAR resulted in significant rCMRglc increases that were maximal by 30 min; by that time, ALCAR 250 produced small, non-significant increase in rCMRglc (no region affected, mean increase 13%) and ALCAR 500 and 750 similar, larger increases in rCMRglc (eight and 11 brain regions affected, mean increases 21 and 22%, respectively). In contrast with ALCAR, carnitine plus acetate did not alter significantly rCMRglc in any brain regions, suggesting that acetate metabolism and carrier are not involved in ALCAR pharmacological activities. ALCAR increased rCMRglc more markedly in subcortical cholinergic (i.e. diagonal band, preoptic magnocellular area) and non-cholinergic (i.e. locus coeruleus, median raphe) nuclei and, to a lesser degree, in limbic and sensorimotor cortical areas. The topographic distribution of rCMRglc increases induced by ALCAR differs from those produced by cholinergic muscarinic agonists and suggest a preferential activation of nicotinic receptors.
Ori
Carlo
C
Department of Anesthesiology, University of Padua, Padua, Italy.
Freo
Ulderico
U
Pizzolato
Gilberto
G
Dam
Mauro
M
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002331:Carnitine / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D007700:Kinetics; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D018697:Nootropic Agents; D000108:Acetylcarnitine; D005947:Glucose; D002331:Carnitine