Behavioural Brain Research 166 (2006) 263–270 Research report Peripubertal anxiety profile can predict predisposition to spatial memory impairments following chronic stress Rudy Bellani a,b,1 , Linda J. Luecken a,2 , Cheryl D. Conrad a,∗ a Department of Psychology, Arizona State University, Box 1104, Tempe, AZ 85287-1104, USA b The Rockefeller University, Box 232, New York, NY 11021, USA Received 29 June 2005; received in revised form 9 August 2005; accepted 10 August 2005 Available online 7 October 2005 Abstract We tested the hypothesis that peripubertal anxiety levels are predictive of the detrimental effects of chronic stress on hippocampal-dependent spatial memory. The anxiety levels of peripubertal male Sprague–Dawley rats (43 days old) were characterized using open field and elevated plus mazes, followed by chronic restraint stress for 6 h/day/21 days beginning in young adulthood (75 days). Following chronic stress treatment, rats were tested on the spatial Y-maze using two inter-trial interval levels of difficulty (4h: 1 day post-chronic stress; 1min: 2 days post-chronic stress). As expected, all groups displayed intact spatial memory in the less difficult 1min version of the Y-maze. However, in the 4h version of the Y-maze, chronically stressed high anxiety rats showed impaired spatial memory, while chronically stressed low anxiety and control (low and high anxiety) rats displayed intact spatial memory. Moreover, a month after chronic stress ended, high anxiety rats had significantly higher basal corticosterone levels than low anxiety rats (control and stress). These results indicate that peripubertal anxiety and chronic stress interact to influence hippocampal-dependent spatial memory in adulthood. © 2005 Elsevier B.V. All rights reserved. Keywords: Restraint; Y-maze; Hypothalamic–pituitary–adrenal axis; Corticosterone 1. Introduction During the last two decades, a large volume of research has demonstrated the deleterious effects of chronic stress on the function of the hippocampus, a region important in memory processing [13,17,35,36,46–48]. Paradigms that repeatedly acti- vate glucocorticoid secretion, such as repeated restraint [5,29], unpredictable stress [52] and psychosocial stressors [22], cause hippocampal-dependent spatial memory deficits, suggesting that exaggerated or prolonged exposure to glucocorticoids is a mech- anism linking chronic stress with hippocampal damage and sub- sequent cognitive impairment. However, the degree of cognitive impairment following chronic stress can vary, with some chroni- cally stressed individuals displaying functional spatial memory, thus suggesting important individual differences [1,12]. ∗ Corresponding author. Tel.: +1 480 965 7761; fax: +1 480 965 8544. E-mail addresses: Rudy.Bellani@mail.Rockefeller.edu (R. Bellani), Linda.luecken@asu.edu (L.J. Luecken), conradc@asu.edu (C.D. Conrad). 1 Tel.: +1 480 313 9326; fax: +1 212 327 8634. 2 Tel.: +1 480 965 6886; fax: +1 480 965 8544. Responsivity to stress may be profiled from behav- ioral phenotype, suggesting that behavioral phenotype may also predict individual cognitive variation following chronic stress. Previous studies have correlated components of the hypothalamic–pituitary–adrenal (HPA) axis with exploration [16] and aggression [54]. Specifically, hyperaggressive mice have higher basal corticosterone and adrenocorticotropic hor- mone levels, sustained elevations of corticosterone following acute stress and increased corticosterone receptor levels com- pared to hypoaggressive mice [54]. Genetically inbred mice and rats also show correlations between HPA axis and behavioral profiles [26,27,53,54]. Yet, anxiety influences exploration [23], locomotion [33] and attack latency [38], and consequently, anx- iety may moderate the correlations between behavior and HPA axis characteristics from previous reports. Therefore, we hypoth- esized that anxiety is a behavioral characteristic that may predict chronic stress reactivity. Puberty is a critical period of HPA axis development [43–45]. Additionally, behavioral phenotype, including anxiety, may per- haps stabilize after, but not before, puberty [11,49]. Indeed, anxiety may be altered by life experiences before puberty [21]. 0166-4328/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2005.08.006