The effects of discontinuing a chronic morphine treatment on the concentrations of glutamate and aspartate were analyzed in the nucleus accumbens of unrestrained unanesthetized rats. The administration of naloxone or the cessation of morphine administration resulted in increased concentrations of glutamate and aspartate in this central nervous system area. These increased amino acid concentrations were observed a few minutes after naloxone administration and persisted in the controls 48 h after the last dose of the opiate. Morphine withdrawal was also studied in rats not injected with naloxone. In these latter animals, increased concentrations of glutamate and aspartate persisted in controls 96 h after the last dose of the opiate. Single doses of morphine, acamprosate or riluzole administered to rats previously withdrawn from chronic morphine treatment restored the amino acid concentrations to normal levels. These results suggest that the maintenance of increased levels of amino acids could be the expression of new adjustments in central nervous system neurotransmission after discontinuation of the chronic morphine treatment.