Attenuation of estrous cycle-dependent marble burying in female rats by acute treatment with progesterone and antidepressants.

Premenstrual dysphoric disorder (PMDD) is characterized by the recurrence of a cluster of physical and negative mood symptoms, especially irritability, appearing when estrogen and progesterone levels decrease during the late luteal phase of the menstrual cycle. The aim of the present study was to explore a new potential model of premenstrual irritability. It has been suggested that burying of harmless objects by rodents may reflect a form of impulsive or anxiety-like behavior. This study demonstrates changes in burying behavior during various phases of the estrous cycle in some but not all female rats. Burying behavior was found to be enhanced at metestrus and decreased at proestrus, characterized by low and high ovarian hormone levels, respectively. No habituation of the cycle-dependent burying was observed. Enhanced burying was not observed in reproductive senescent and ovariectomized females characterized by stable, low levels of ovarian hormones. Increased marble burying at metestrus was reversed by acute treatment with antidepressants fluoxetine, desipramine, nomifensine, the benzodiazepine agonist diazepam, and progesterone, while the neuroleptic chlorpromazine was without effect. Reversal of cycle-dependent burying was unrelated to the drugs' effects on locomotor activity. These results indicate that estrous cycle-dependent marble-burying behavior displayed by a subgroup of female rats might be a manifestation of ovarian hormone-dependent irritability. This manifestation may be used to elucidate the neuroendocrine mechanisms triggering premenstrual irritability, and the detailed mode of action of antidepressants when used for PMDD.