Depression and poor sleep: The effect of monoaminergic antidepressants in a pre-clinical model in rats

The effects of five antidepressants (escitalopram, paroxetine, duloxetine, venlafaxine, and reboxetine) on the sleep architecture were investigated in freely moving rats in the light phase of a 12:12 h light:dark cycle following a single i.p. dose of antidepressant. Overall, paroxetine and escitalopram exhibited the least sleep disruptive profiles, whereas duloxetine, venlafaxine, and reboxetine increased the time spent awake and suppressed paradoxical sleep. Analysis of the EEG at 1 h intervals revealed only subtle differences from the overall picture. The effect of venlafaxine on disruption of sleep architecture could not be readily explained by its in vitro serotonin (5-HT) and noradrenaline (NA) reuptake inhibitory potencies. In vivo microdialysis experiments in the ventral hippocampus of freely moving rats revealed that venlafaxine affected the 5-HT and NA systems equally at the doses tested. Duloxetine (7.7 mg/kg) induced maximal blockade of the 5-HT transporter and duloxetine 7.7 mg/kg also modulated the noradrenaline system. Thus, in this animal model, the enhancement of noradrenergic activity is more disruptive on the sleep architecture than enhancement of serotonergic activity.