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.
Laboratory of Psychopharmacology, Research Institute of Pharmacology, Volgograd Medical Academy, Pavshih Bortsov sq. 1, 400131, Volgograd, Russian Federation.
V I
VI
Petrov
V S
VS
Sergeyev
N V
NV
Onishchenko
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