Males and females respond differently to controllability and antidepressant treatment.
BACKGROUND
Women are much more likely to suffer from stress-related mental illness than men; yet few, if any, animal models for such sex differences exist. Previously, we reported that exposure to an acute stressor enhances learning in male rats yet severely impairs learning in female rats. Here, we tested whether these opposite effects in males versus females could be prevented by establishing control over the stressor or by antidepressant treatment.


METHODS
Learning was assessed using the hippocampal-dependent task of trace eyeblink conditioning. In the first experiment, groups of male and female rats were exposed to controllable or uncontrollable stress and trained. In a second experiment, they were exposed to an uncontrollable stressor after chronic treatment with the antidepressant fluoxetine (Prozac). In a final experiment, females were exposed to uncontrollable stress after acute treatment with fluoxetine.


RESULTS
Establishing control over the stressful experience eliminated the detrimental effect of stress on learning in females as well as the enhancing effect of stress in males. Moreover, chronic but not acute treatment with fluoxetine prevented the learning deficit in females after exposure to stress. Treatment with fluoxetine did not alter the male response to stress.


CONCLUSIONS
These data indicate that males and females not only respond in opposite directions to the same stressful event but also respond differently to controllability and antidepressant treatments.
Leuner
Benedetta
B
Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 153 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Mendolia-Loffredo
Sabrina
S
Shors
Tracey J
TJ
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D003215:Conditioning, Eyelid / Q000187:drug effects*; D004334:Drug Administration Schedule; D004576:Electromyography / Q000187:drug effects / Q000379:methods; D004597:Electroshock / Q000009:adverse effects; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012149:Restraint, Physical / Q000379:methods; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology
D000928:Antidepressive Agents; D005473:Fluoxetine