Effects of acute and chronic treatment with amoxapine and cericlamine on the sleep-wakefulness cycle in the rat

Antidepressant drugs, such as the tricyclics and the serotonin reuptake inhibitors, are well known to decrease paradoxical sleep and occasionally increase slow wave sleep in human and in Animals. In order to examine whether amoxapine (a mixed NA reuptake blocker and 5-HT2/5-HT3 antagonist) and cericlamine (a selective 5-HT reuptake inhibitor) exert the same effect in rats, and to investigate the possible relationships between sleep, the action of antidepressants and the serotoninergic system, the effects of these two different drugs were examined under acute and chronic conditions. Acutely, amoxapine (1, 5 and 10 mg/kg; i.p.) and cericlamine (1, 8, 16 and 32 mg/kg; i.p.) decreased paradoxical sleep and increased deep slow wave sleep especially when they were given at a low dose. When administered for 14 days, amoxapine induced a sustained decrease of paradoxical sleep during the whole treatment, while some tolerance was observed with regard to the inhibitory effect of cericlamine on this state of sleep. In addition, a rebound of paradoxical sleep occurred on the first day of cericlamine withdrawal. Thus, amoxapine and cericlamine exerted the same effects on the states of vigilance in the rat as do other antidepressants. The effects of cericlamine on sleep probably reflect its blocking action on 5-HT uptake, whereas the more complex effects of amoxapine might involve its 5-HT2/5-HT3 antagonist properties.