Chronic stress is associated with the development of anxiety and depression. Moreover, phosphodiesterase-4 (PDE-4) has been implicated in the pharmacological effects of antidepressants. In this study, we investigated the effects of the PDE-4 inhibitor rolipram on abnormalities of emotional behavior induced by chronic restraint stress (CRS) in mice.
For exposing CRS, mice were restrained in a 50mL syringe with numerous small breathing holes for 3 hours a day for 10 consecutive days. Rolipram (1.25 mg/kg, i.p.), fluvoxamine (a SSRI, 30 mg/kg, p.o.) to evaluate the predictive validity of an animal model for depression, or vehicle were administered one hour before the restraint stress.
In mice subjected to CRS, time spent in the open arm of the elevated plus-maze, as well as the time spent in the central area of the open field apparatus decreased, indicating anxiogenic behavior. Furthermore, in the forced swim test, immobility time increased in mice exposed to CRS, implying depressive-like behavior. These behavioral abnormalities in CRS mice were ameliorated by both fluvoxamine and rolipram administered prior to restraint stress.
These results suggest that mice exposed to CRS have validity as an animal model for depression and PDE-4 may be involved in the development of anxiety-like and depression-like behaviors induced by CRS.