It is known that during perimenopause, women may over react to stressful situations. This study was designed to substantiate if this over reaction is observed in an animal model of perimenopause i.e. rats treated with 4-vinylcyclohexene diepoxide (VCD).

Female rats from 28 days old were injected (SC) daily with VCD (160 mg/kg, diluted in corn oil 2.5 µl/g BW; VCD group) or Corn oil (2.5 µl/g BW, Control group) for 15 days. At 85 days of age following assessment of estrous cyclicity, external jugular vein was cannulated in the afternoon of metestrus phase and in next morning (diestrus) at 10.00 h, rats in both groups were subjected to 30 min restraint stress. Blood samples were withdrawn before (-5 min), during (2, 5, 15, 30 mins), and after (45, 60, 90 mins) restraint stress to evaluate the secretion of 3 stress responsive hormones. After the last sampling, animals were perfused and brains processed immunohistochemically for c-FOS expression in the noradrenergic neurons of Locus Coeruleus (LC) to evaluate the central response to stress.

Basal secretion of prolactin, corticosterone, and progesterone was similar in both groups. Prolactin concentration was higher (P < 0.05) during stress (5 and 15 mins); Corticosterone concentration was higher (P < 0.05) during recovery (45, 60, and 90 mins) in VCD rats compared to Control rats. The total amount of Progesterone secretion on the other hand, was lower (P < 0.05) in VCD vs Control rats. The increase in the number of c-FOS/Tyrosine Hydroxylase immunoreactive neurons induced by stress was higher (P < 0.05) in VCD compared to the Control rats.

These results show that central as well as peripheral components of the stress systems are overactive in VCD treated rats. Thus, this animal model seems suitable to investigate behavioural changes that occur during perimenopause in women.