Antidepressant effects of rolipram in a genetic animal model of depression: cholinergic supersensitivity and weight gain.

The effects of rolipram, a new generation antidepressant which is a selective inhibitor of phosphodiesterase, on the selectively bred Flinders Sensitive Line (FSL) of rats, a genetic animal model of depression, was studied. Acutely, rolipram produced comparable decreases in temperature and activity in the FSL and the Flinders Resistant Line (FRL) rats. Upon chronic treatment there was a trend for rolipram to counteract the shock-induced suppression of activity in the FSL rats, suggesting an antidepressant-like effect. However, both groups gained a significant amount of weight, which appeared to be associated with polydipsia and polyuria. In addition, both groups were significantly more affected by the muscarinic agonist, oxotremorine, than their vehicle-treated counterparts. Thus, the FSL rats, which are genetically supersensitive to cholinergic agonists, are even more sensitive following chronic treatment with rolipram. These unexpected findings suggest that rolipram may not be appropriate as an antidepressant for humans because of undesirable side effects.