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Acute Increase of the Glutamate–Glutamine Cycling in Discrete Brain Areas after Administration of a Single Dose of Amphetamine
Author(s) -
Pereira Frederico C.,
Rolo Marta R.,
Marques Elsa,
Mendes Vera M.,
Ribeiro Carlos F.,
Ali Syed F.,
Morgadinho Teresa,
Macedo Tice R.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1432.040
Subject(s) - glutamate receptor , glutamine , glutamatergic , gabaergic , chemistry , neurotoxicity , amphetamine , dopamine , pharmacology , gamma aminobutyric acid , hippocampus , medicine , endocrinology , inhibitory postsynaptic potential , biology , biochemistry , amino acid , toxicity , receptor , organic chemistry
The glutamate–glutamine cycle between neurons and glia is tightly related to excitatory glutamatergic and inhibitory GABAergic regulation in brain. The role of this neuron–astrocyte cross‐talk on the neurotoxicity induced by amphetamines is not understood. Also, the impact of neurotoxic doses of amphetamines on the balance between glutamatergic and GABAergic circuits is largely unknown. The aim of this work was to assess the acute effect of a neurotoxic regimen of amphetamine (AMPH) on glutamine (GLN, an astrocytic marker) levels and on glutamine/glutamate (an index for glutamate–glutamine cycle) and GABA/glutamate ratios in rat brain. Sprague‐Dawley rats were sacrificed 4 and 24 h after a single‐dose regimen of AMPH (30 mg/kg, i.p.), and the caudate–putamen (CPu), frontal cortex (FC), and hippocampus (Hp) were dissected for analysis of glutamate (GLU), γ‐aminobutyric acid (GABA), and GLN. The total content of these amino acids was measured using a microbore HPLC electrochemical detector. Although AMPH did not change GLU levels, it increased both GLN content and GLN/GLU ratio (160–469%) at 4 h, but not at 24 h, in all regions after injection. Striatal GABA levels and GABA/GLU ratio were increased (46 and 100%, respectively) at 24 h. In hippocampus the GABA/GLU increase (60%) occurred as early as 4 h after treatment. To the contrary, AMPH exerted no effect in GABA/GLU balance in frontal cortex. These data strongly suggest that this neurotoxic AMPH regimen provoked an early increase in the glutamate–glutamine cycle between neurons and glia. This increase may ultimately lead to an upregulation of the inhibitory system as a compensatory response.