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Acute Increase of the Glutamate-Glutamine Cycling in Discrete Brain Areas after Administration of a Single Dose of Amphetamine
- Source :
- Annals of the New York Academy of Sciences. 1139:212-221
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- 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), gamma-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.
- Subjects :
- Male
medicine.medical_specialty
Glutamine
Glutamic Acid
Glutamate-glutamine cycle
Hippocampus
Biology
General Biochemistry, Genetics and Molecular Biology
Rats, Sprague-Dawley
Glutamatergic
History and Philosophy of Science
Internal medicine
medicine
Animals
Amphetamine
gamma-Aminobutyric Acid
Neurons
General Neuroscience
Putamen
Glutamate receptor
Neurotoxicity
Brain
medicine.disease
Frontal Lobe
Rats
Endocrinology
nervous system
Biochemistry
Astrocytes
GABAergic
Central Nervous System Stimulants
Caudate Nucleus
medicine.drug
Subjects
Details
- ISSN :
- 17496632 and 00778923
- Volume :
- 1139
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi.dedup.....f5078fd577d82924ddd996461a84a610
- Full Text :
- https://doi.org/10.1196/annals.1432.040