DMBA-induced mammary tumor growth in rats exhibiting increased or decreased ability to cope with stress due to early postnatal handling or antidepressant treatment

Depression and an ability to cope with stress are suggested to play a role in the vulnerability to breast cancer. In rats, neonatal clomipramine administration induces subsequent behavioral abnormalities that closely resemble those seen in human endogenous depression. Early postnatal handling, on the other hand, improves subsequent ability to cope with stress in rodents. The present study examined whether early clomipramine treatment or handling influences the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Between postnatal days 5 and 20, rat pups were injected daily with 25 mg/kg clomipramine, handled either by holding them in a hand (H-handling) or by giving them a saline injection (I-handling), or left nonhandled. During these manipulations, but not later, body weight gain was lower in the I-handled and clomipramine-treated pups than in the H-handled rats. As adults, the time spent immobile in the swim test, a model of depressive behavior and an ability to cope with stress, was significantly lengthened in the clomipramine-treated female rats, and shortened in the handled females. Measurement of plasma 17-β-estradiol (E2) did not reveal any significant differences between the groups. The percentage of animals developing mammary tumors was significantly higher, and the length of survival shorter among the clomipramine-treated rats than among the I-handled rats. However, both groups exhibited less tumors and longer survival than the nonhandled controls. There were no differences in mammary tumor incidence or survival between the nonhandled and H-handled rats. These findings indicate that DMBA-induced tumor growth is increased in animals that receive early postnatal clomipramine treatment and subsequently exhibit increased depressive tendencies. However, an improved ability to cope with stress was not directly related to tumor growth. Although immobility in the swim test was shortened in both groups of handled animals, only those animals that were handled to receive a daily saline injection showed reduced tumor growth. This suggests that early weight gain, which was high in the H-handled and low in the I-handled rats, may play a critical intervening role in mediating the effects of neonatal handling on subsequent mammary tumorigenesis.