Adaptation of female rats to stress: shift to male pattern by inhibition of corticosterone synthesis.

In a previous study, male rats showed behavioural deficits after a single restraint stress but not after 5 daily restraint periods (i.e. adaptation had developed): female rats although less affected by single restraint failed to adapt over the same time course. This sex difference was associated with the male but not the female rats showing enhanced behavioural responses to the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) after 5 restraint periods. In the present study, the role of the greater increases of plasma corticosterone in stressed females in these sex differences was studied. The corticosterone synthesis inhibitor metyrapone (75 mg/kg i.p.) was given to attenuate the rise of corticosterone to a level typical of stressed males. This resulted in the behavioural deficits of the female rats being shifted in the direction of the male pattern. Thus, their deficits in open field activity and food intake after single and repeated stresses were potentiated and opposed respectively. The latter effect was associated with increased responses to 5-MeODMT. Metyrapone alone was without significant effect. Brain regional 5-HT metabolism was unaffected. The results are consistent with corticosterone facilitating adaptation to single restraint but impairing adaptation to repeated restraint. As failure to adapt to repeated stress is an animal model of depression, results as a whole suggest that increased corticoid levels and decreased 5-HT functional activity may have a role in the development of the illness and its greater incidence in women.