Chronic variable stress facilitates tumoral growth: reversal by imipramine administration

The present study was conducted to examine whether a chronic variable stress procedure (CVS)--an animal model of depression--facilitates tumor growth, and whether this effect can be modified by concurrent administration of the antidepressant imipramine (IMI). Unstressed rats, with or without previous administration of the immunosuppressive agent cyclosporine (CS), were inoculated with 5 x 10(6) cells of a sarcoma. Another group of rats was inoculated with tumoral cells and later exposed to the CVS procedure with or without concurrent administration of IMI (10 mg/kg, i.p.). An additional group of animals was treated with CS and later given daily injections of IMI (10 mg/kg, i.p.) without stress manipulation. A lack of tumoral development was observed in unstressed animals without previous injections of CS, whereas, prior injections of this immunosuppressive agent increased tumoral growth in unstressed animals. Exposure to the CVS procedure facilitated tumoral growth even in animals without CS injections. This effect was clearly attenuated when chronically stressed rats were concurrently given IMI. These findings support the notion that the development of a tumoral process is facilitated when a state of experimental depression is induced and that the reversal of such a state by antidepressant treatment results in the inhibition of tumor development.