Combined effects of diazepam and melatonin in two tests for anxiolytic activity in the mouse

The effects of behaviorally nonactive doses of melatonin and diazepam were investigated in two test models for anxiolytics in mice to see whether mutual enhancement could be observed when the two treatments were combined. The test models used were the four plates test and the tail suspension test. In the former test anxiolytics increase the number of punished crossings and in the latter increase the duration of immobility of mice suspended by the tail. In the four plates test combined treatment with melatonin (128 and 256 mg/kg IP) and diazepam (0.5 mg/kg PO) caused a significant increase in the number of punished crossings, whereas each treatment alone was without effect. Similarly, in the tail suspension test, a clear increase in the duration of immobility was observed after combined treatment (256 mg/kg IP melatonin + 0.5 mg/kg PO diazepam), whereas no effects were observed with the individual treatments alone. These results suggest that melatonin can enhance the anxiolytic actions of diazepam.