Women are more likely than men to suffer from stress-related mental disorders, such as depression. In the present experiments, we identified sex differences in one of the most common animal models of depression, that of learned helplessness. Male and female rats were trained to escape a mild footshock each day for 7 days (controllable stress). Each rat was yoked to another rat that could not escape (uncontrollable stress), but was exposed to the same amount of shock. One day later, all stressed rats and unstressed controls were tested on a more difficult escape task in a different context. Most males exposed to uncontrollable stress did not learn to escape and were therefore helpless. In contrast, most females did learn to escape on the more difficult escape task, irrespective of whether they had been exposed to controllable or uncontrollable stress. The sex differences in helplessness behavior were not dependent on the presence of sex hormones in adulthood, because neither ovariectomy of females nor castration of males abolished them. The absence of helplessness in females was neither dependent on organizational effects of testosterone during the day of birth, because masculinized females did not express helplessness as adults. Thus, sex differences in helplessness behavior are independent of gonadal hormones in adulthood and testosterone exposure during perinatal development. Learned helplessness may not constitute a valid model for depressive behavior in women, at least as reflected by the response of female rats to operant conditioning procedures after stressful experience.

Background-Numerous studies have implicated neurogenesis in the hippocampus in animal models of depression, especially those related to controllability and learned helplessness. Here, we tested the hypothesis that uncontrollable, but not controllable stress would reduce cell proliferation in the hippocampus of male and female rats, and would relate to the expression of helplessness behavior.

Previous research has shown that some associative learning tasks prevent the death of new neurons in the adult hippocampus. However, it is unclear whether it is mere exposure to the training stimuli that rescues neurons or whether successful learning of the task is required for enhanced neuronal survival. If learning is the important variable, then animals that learn better given the same amount of training should retain more of the new cells after learning than animals that do not learn as well.Here we examined the effects of training versus learning on cell survival in the adult hippocampus. Animals were injected with BrdU to label a population of cells and trained one week later on one of two trace conditioning tasks, one of which depends on the hippocampus and one that does not. Increases in cell number occurred only in animals that acquired the learned response, irrespective of the task. There were significant correlations between acquisition and cell number, as well as between asymptotic performance and cell number. These data support the idea that learning and not simply training increases the survival of the new cells in the hippocampus.