Abstract
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.
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Acknowledgements
This work was supported by National Institutes of Health (National Institute of Mental Health 59970) and National Science Foundation (Integrative Organismal Systems 0444364) to Dr Tracey J Shors. This research was supported by a Marie Curie International Fellowship to Dr Christina Dalla, within the sixth European Community Framework Programme.
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There is no conflict of interest for the present work.
Over the past 3 years the authors have received compensation for professional services:
Professor TJ Shors: Rutgers The State University of New Jersey, National Institutes of Health, National Science Foundation and National Alliance for Research on Schizophrenia and Depression.
Dr Christina Dalla: Rutgers The State University of New Jersey, National Institutes of Health and National Science Foundation, University of Athens/Greece, European Commission (Marie Curie Outgoing Individual Fellowship).
Carol Edgecomb BS: Rutgers The State University of New Jersey, National Institutes of Health and National Science Foundation.
Abigail S Whetstone: Rutgers The State University of New Jersey.
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Dalla, C., Edgecomb, C., Whetstone, A. et al. Females do not Express Learned Helplessness like Males do. Neuropsychopharmacol 33, 1559–1569 (2008). https://doi.org/10.1038/sj.npp.1301533
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