This study investigated the effects of REM (rapid eye movement) sleep deprivation (RSD) on the activity of central cholinergic receptors and passive avoidance retention in rats treated neonatally with clomipramine. Male rat pups treated with clomipramine (15 mg/kg, s.c.) twice daily from postnatal day 5 to 21 were subjected to RSD procedure at three months of age, for 4 days consecutively. In the post-RSD phase, RSD-control rats showed a significantly enhanced cholinomimetic-induced hypothermia and an improved retention in passive avoidance task. However, these measures were not significantly different in RSD-experimental group as compared to rats treated neonatally with saline. These results suggest that RSD reverses the sensitivity of central cholinergic receptors in rats given clomipramine neonatally, and this mechanism may be involved in mediating the antidepressant effects of RSD treatment in clomipramine model of depression.