Ovarian hormones modulate ‘compulsive’ lever-pressing in female rats

Life events related to the female hormonal cycle may trigger the onset of obsessive–compulsive disorder (OCD) or exacerbate symptoms in women already suffering from it. These observations suggest a possible role for ovarian hormones in the course of this disorder. Yet, the mechanisms that may subserve the modulatory effect of ovarian hormones are currently unknown. The aim of the present study was therefore to test the role of ovarian hormones in the signal attenuation rat model of OCD. Experiment 1 compared the behavior of pre-pubertal and adult male and female rats in the model, and found no age and sex differences in compulsive responding. Experiment 2 found that compulsive responding fluctuates along the estrous cycle, being highest during late diestrous and lowest during estrous. Acute administration of estradiol to pre-pubertal female rats was found to attenuate compulsive behavior (Experiment 3), and withdrawal from chronic administration of estradiol was shown to increase this behavior (Experiment 4). These findings extend the use of the signal attenuation model of OCD to female rats, and by demonstrating that the model is sensitive to the levels of ovarian hormones, provide the basis for using the model to study the role of ovarian hormones in OCD. In addition, the present findings support the hypothesis that the increased risk of onset and exacerbation of OCD in women post-partum may be a result of the decrease in the level of estradiol, which was elevated during pregnancy.