Effect of Precipitated Withdrawal on Extracellular Glutamate and Aspartate in the Nucleus Accumbens of Chronically Morphine-Treated Rats: An In Vivo Microdialysis Study

Abstract

Excitatory amino acids release during morphine or naloxone administration was studied in rats. Microdialysis in freely moving animals and capillary electrophoresis with laser-induced fluorescence detection were used to measure several amino acids including glutamate and aspartate in the extracellular fluid at the nucleus accumbens. Perfusion with a calcium-free Ringer’s solution decreased glutamate and aspartate in nucleus accumbens dialysates to 35% of its baseline levels, suggesting partial synaptic origin of these amino acids. The first morphine injection decreased glutamate and aspartate to 50% of its baseline level. After repeated morphine injections this effect disappeared, suggesting tolerance. Naloxone injections to morphine-dependent rats increased 300% glutamate and aspartate release; these experiments suggest that excitatory amino acid release in the nucleus accumbens might play a role in morphine withdrawal.