EFFECTS OF ION-CHANNEL BLOCKERS ON RAPID POSTMORTEM CHANGES IN EXTRACELLULAR DOPAMINE AND SEROTONIN LEVELS IN THE RAT NUCLEUS-ACCUMBENS

In the present study, we used in vivo brain microdialysis to examine t he effects of ion channel blockers tetrodotoxin (TTX), EGTA-free Ca2and verapamil on rapid post mortem changes in extracellular levels of doapmine (DA), serotonin (5-HT) and their metabolites dihydroxyphenyla cetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in the ACC of freely moving rats. Extracellular ACC DA levels decreased following the perfusion of the three ion channel blockers in freely moving rats , and then, at death by cervical dislocation, maximum respective 220-, 60- and 90-fold increases were observed in the extracellular output o f DA in animals treated with EGTA, verapamil and TTX, respectively. Al so, ACC 5-HT decreased following perfusion with the three blockers in the freely moving rats, and then maximum increases of 80-, 30- and 45- fold in the extracellular output of 5-HT were observed at death in ani mals treated with EGTA, verapamil and TTX, respectively, compared to t he baseline. Cervical dislocation-induced rapid postmortem changes wer e inhibited markedly by perfusion with CSF containing the Ca2+ entry b locker verapamil. These observations suggested that rapid postmortem c hanges in ACC DA and 5-HT release were associated with the action of c alcium ion channels and/or voltage gated channels in the CNS. (C) 1997 Elsevier Science Ireland Ltd.