Chronic stress, cyclic 17β-estradiol, and daily handling influences on fear conditioning in the female rat

• Published in: Neurobiology of learning and memory 2010-10, Vol.94 (3), p.422-433
• Main Authors: Hoffman, Ann N., Armstrong, Charles E., Hanna, Jeffery J., Conrad, Cheryl D.
• Format: Article
• Language: English
• Subjects: Amygdala; Analysis of Variance; Animals; Association Learning - drug effects; Association Learning - physiology; Behavioral psychophysiology; Biological and medical sciences; Chronic stress; Conditioning, Classical - drug effects; Conditioning, Classical - physiology; Electroshock; Estradiol - administration & dosage; Estrogen; Extinction; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fear - drug effects; Fear - physiology; Fear conditioning; Female; Freezing Reaction, Cataleptic - drug effects; Freezing Reaction, Cataleptic - physiology; Fundamental and applied biological sciences. Psychology; Handling; Ovariectomy; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Restraint; Restraint, Physical; Stress, Physiological - physiology
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2010.08.010

► Chronic stress facilitates the acquisition of fear conditioning in OVX or gonadally-intact female rats. ► 17β-estradiol has no influence on cued fear conditioning in OVX female rats. ► Daily handling interacts with chronic stress to enhance the acquisition of fear conditioning further in female rats Chronic stress and estrogens alter many forebrain regions in female rats that affect cognition. In order to investigate how chronic stress and estrogens influence fear learning and memory, we ovariectomized (OVX) female Sprague–Dawley rats and repeatedly injected them (s.c.) with 17β-estradiol (E, 10μg/250g or sesame oil vehicle, VEH). Concurrently, rats were restrained for 6h/d/21d (STR) or left undisturbed (CON). Rats were then fear conditioned with 4tone-footshock pairings and then after 1h and 24h delays, given 15tone extinction trials. Regardless of E treatment, chronic stress (VEH, E) facilitated freezing to tone during acquisition and extinction following a 1h delay, but not during extinction after a 24h delay. E did not influence freezing to tone during any phase of fear conditioning for either the control or chronically stressed rats, but did influence contextual conditioning that may have been carried predominately by the STR group. In the second experiment, we investigated “handling” influences on fear conditioning acquisition, given the disparate findings from the current study and previous work (Baran, Armstrong, Niren, & Conrad, 2010; Baran, Armstrong, Niren, Hanna, & Conrad, 2009). Female rats remained gonadally-intact since E did not influence tone fear conditioning. Indeed, brief daily handling (1–3m/d/21d) facilitated acquisition of fear conditioning in chronically stressed female rats, and either had no effect or slightly attenuated fear conditioning in controls. Thus, chronic stress impacts amygdala-mediated fear learning in both OVX- and gonadally-intact females as found previously in males, with handling significantly influencing these outcomes.