The toxicity profile of a single dose of paroxetine: An alternative approach to acute toxicity testing in the rat

In this study we have examined the effect of a single administration of the selective serotonin reuptake inhibitor, paroxetine (120-300 me kg(-1), ora lly) in a recently developed rodent model of acute toxicity testing. Reduce d body-weight, food consumption, water consumption and body temperature wer e observed in all paroxetine-treated groups, which were reversible within 7 days. Five days after administration, a dose-dependent increase in red blo od cells, haemoglobin and haematocrit was observed with the 3 higher dose l evels of paroxetine, which was significant in the 240 and 300 mg kg(-1) tre atment groups (P<0.05). Hyperactivity was apparent in the first 24 hr follo wing treatment, as was evidence of the serotonin syndrome. When the animals were sacrificed (11 days after drug administration), an increase in liver weight was observed in the highest dose. These results are in agreement wit h those previously observed with paroxetine at the preclinical and clinical levels. They demonstrate that this rodent model, because of its multi-para meter nature, is a useful method for examining the consequences of a single high dose of an antidepressant drug.