REVIEW ARTICLE Chronic Stress and Neural Function: Accounting for Sex and Age V. N. Luine,* K. D. Beck, à R. E. Bowman,§ M. Frankfurt– and N. J. MacLusky** *Department of Psychology, Hunter College of CUNY, New York, NY, USA.  VA NJ Health Care System, East Orange, NJ, USA. àDepartment of Neuroscience, UMDNJ, Newark, NJ, USA. §Department of Psychology, Sacred Heart University, Fairfield, CT, USA. –Department of Physiology ⁄ Pharmacology, CUNY Medical School, New York, NY, USA. **Department of Biochemistry, Ontario Veterinary College, Guelph, ON, Canada Beginning with Selye’s seminal studies (1), stress-dependent responses have been considered to follow a temporal pattern of response in which short-term stressors evoke adaptive changes by the organism whereas long-term stressors (chronic stress) cause maladaptive changes. Recent studies report that neural functions such as cognition and anxiety also follow this temporal pattern of response in rats. However, this review highlights other recent stud- ies from our own and other laboratories examining the effects of chronic stress in female as well as male subjects during develop- ment (prenatally), adulthood and old age. These studies show a more complex pattern of responses to chronic stress for cognition and anxiety and suggest that neural stress responses are dependent on the sex, age and gonadal hormone status of subjects. Chronic stress effects on cognitive function are different in the sexes Similar to its deleterious effects on several physiological systems, chronic stress also exerts damaging effects in the central nervous system. A broad range of studies show that neurones are adversely Journal of Neuroendocrinology Correspondence to: Dr Victoria Luine Department of Psychology, Hunter College of CUNY, 695 Park Ave, New York, NY 10021, USA (e-mail: vluine@hunter.cuny.edu). Cognitive responses to stress follow the temporally dependent pattern originally established by Selye (1) wherein short-term stressors elicit adaptive responses whereas continued stress (chronic) results in maladaptive changes – deleterious effects on physiological systems and impaired cognition. However, this pattern for cognitive effects appears to apply to only half the population (males) and, more specifically, to young, adult males. Females show different cogni- tive responses to stress. In contrast to impaired cognition in males after chronic stress, female rodents show enhanced performance on the same memory tasks after the same stress. Not only cognition, but anxiety, shows sex-dependent changes following chronic stress – stress is anxio- lytic in males and anxiogenic in females. Moreover, behavioral responses to chronic stress are different in developing as well as aging subjects (both sexes) as compared to adults. In aged rats, chronic stress enhances recognition memory in both sexes, does not alter spatial memory, and anxiety effects are opposite to young adults. When pregnant dams are exposed to chronic stress, at adulthood the offspring display yet different consequences of stress on anxiety and cognition, and, in contrast to adulthood when the behavioral effects of stress are reversible, pre- natal stress effects appear enduring. Changing levels of estradiol in the sexes over the lifespan appear to contribute to the differences in response to stress. Thus, theories of stress dependent moduations in CNS function – developed solely in male models, focused on peripheral physiolo- gical processes and tested in adults – may require revision when applied to a more diverse population (age- and sex-wise) at least in relation to the neural functions of codnition and anxiety. Moreover, these results suggest that other stressors and neural functions should be investigated to determine whether age, sex and gonadal hormones also have an impact. Key words: anxiety, memory, oestradiol, sex differences, stress. doi: 10.1111/j.1365-2826.2007.01594.x Journal of Neuroendocrinology 19, 743–751 ª 2007 The Authors. Journal Compilation ª 2007 Blackwell Publishing Ltd