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Effect of Acetyl‐L‐Carnitine (ALCAR) on the Striatal Outflow of Various Neurotransmitters Using Microdialysis and the Role of the GLT‐1/EAA‐2 Glutamate Transporter During Middle Cerebral Artery Occlusion (MCAO) in Rats
Author(s) -
Jalal Fakhreya Yousuf,
Böhlke Mark,
Maher Timothy J.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.746.5
Subject(s) - microdialysis , taurine , neuroprotection , chemistry , glutamate receptor , neurotransmitter , dopamine , pharmacology , medicine , endocrinology , serotonin , extracellular fluid , extracellular , biochemistry , amino acid , receptor
We have shown that ALCAR is neuroprotective in rat models of ischemia. This study determined ALCAR's effect on extracellular fluid (ECF) neurotransmitters that are disrupted during ischemia. Using striatal microdialysis we measured ALCAR's effect on MCAO‐induced alterations in ECF dopamine (DA), serotonin (5HT), and their major metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC), 4‐hydroxy‐3‐methoxyphenylacetic acid (HVA), and 5‐hydroxyindolacetic acid (5‐HIAA), as well as glutamate (GLU), GABA and taurine (TAU). ECF GLU was also monitored in the presence of dihydrokainate (DHK), a GLT‐1/EAA‐2 inhibitor before, and during permanent intraluminal MCAO. A marked decrease of DA, 5‐HT and their metabolites was observed during MCAO. The amino acids also greatly increased, likely reflecting massive neuronal cell death. Chronic pretreatment with ALCAR (400mg/kg/5days, i.p) attenuated the decrease in DA, DOPAC, HVA, 5‐HIAA (p<0.05), while the ECF level of 5‐HT was unaltered. ALCAR also attenuated the expected increase in GLU, GABA and TAU (p<0.01). In the presence of DHK, ECF GLU significantly increased in both control and ALCAR‐treated groups. The neuroprotection of ALCAR may partly result from restoration of the balance between excitatory and inhibitory neurotransmitters, especially via a reduction in GLU accumulation by modulation of GLT‐1 transporters.