The effect of N-acetyl-L-aspartic acid dilithium salt on dopamine release and synthesis in the rat striatum in vivo.
The effect of the dilithium salt of N-acetyl-L-aspartic acid on release and synthesis of dopamine in the striatum was investigated using microdialysis in freely moving rats. Intrastriatal infusion of 1 mM N-methyl-D-aspartate, an NMDA receptor agonist, augmented extracellular dopamine to 215% of baseline, while 1 mM dilithium N-acetyl-L-aspartate increased dopamine release to 190% of baseline in rat striatum. Infusion of DL-2-amino-5-phosphonopentanoic acid, a competitive NMDA receptor antagonist, prior to infusion of dilithium N-acetyl-L-aspartate did not significantly alter basal levels of dopamine, but reversed the dilithium N-acetyl-L-aspartate-evoked elevation in extracellular dopamine. Intrastriatal perfusion with 6-cyano-7-nitroquinoxaline-2,3-dione, an AMPA/kainate receptors antagonist, altered neither basal levels of dopamine nor dilithium N-acetylaspartate-induced dopamine release. When the striatum was continuously perfused with the inhibitor of L-aromatic amino acid decarboxylase, 3-hydroxybenzylhydrazine dihydrochloride (100 microM), both dilithium N-acetylaspartate and NMDA added to the perfusate increased extracellular 3,4-dihydroxyphenyl-L-alanine, reflecting the effect of the compounds on the biosynthesis of dopamine. The data suggest that availability of dilithium N-acetyl-L-aspartate to activate dopamine turnover and release in the rat striatum may be mediated by presynaptic NMDA heteroreceptors located at dopaminergic neurons.
Petrov
V I
VI
Laboratory of Psychopharmacology, Research Institute of Pharmacology, Volgograd Medical Academy, Pavshih Bortsov sq. 1, 400131, Volgograd, Russian Federation.
Sergeyev
V S
VS
Onishchenko
N V
NV
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001224:Aspartic Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C000179:N-acetylaspartate; D004298:Dopamine