A COMPARISON OF THE ACUTE AND CHRONIC EFFECTS OF ANTIDEPRESSANTS IN CULTURED C6 AND 1321N1 CELLS

The cytotoxicities of the antidepressants amitriptyline, imipramine (b oth tricyclic), fluoxetine (a selective serotonin re-uptake inhibitor) and tranylcypromine (a monoamine oxidase inhibitor) were compared in vitro in rat (C6) glioma and human (1321N1) astrocytoma cell lines. Di fferences in toxicity were determined after acute (24-hour) and chroni c (7-day) administration and assessed by using the neutral red uptake (NRU) assay, the MTT assay, increased expression of glial fibrillary a cidic protein (GFAp), and reactive morphology criteria. The relative t oxicities (EC50 [concentration causing an effect in 50% of cells] valu e range) were fluoxetine > amitriptyline > imipramine > tranylcypromin e for ail the tests employed, in both cell lines and at both exposure times. There was a high and significant positive correlation between t he different cell types, at both exposure times, with both the NRU and MTT assays. Increases in MTT reduction, NRU, and GFAp expression asso ciated with cell activation were noted in C6 cells after exposure for 24 hours, but decreased after exposure for 7 days. For 1321N1 cells, i ncreases in NRU were only observed after exposure for 24 hours. Reacti ve-type changes in morphology were seen after exposure to all the anti depressants, in both the C6 and 1321N1 cell lines. The data show that low concentrations of antidepressants induce metabolic changes in the astrocyte cell lines, with some significant differences in the pattern s of toxicity of the tested substances.