Sex differences in the pituitary-adrenal response following acute antidepressant treatment in sheep.

RATIONALE

Depression is more prevalent in women than in men, and therapeutic responses may also differ between the sexes. In addition, abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is more common in depressed women.

OBJECTIVES

To further examine these phenomena, the present study was designed to investigate whether sex differences exist in the HPA axis responses of male and female sheep following acute antidepressant administration.

METHODS

Two commonly prescribed antidepressants, imipramine (a tricyclic antidepressant, TCA; 2.0 and 5.0 mg/kg) and sertraline (a selective serotonin reuptake inhibitor, SSRI; 0.5, 2.0 and 5.0 mg/kg) were administered to gonadectomized male and female sheep via acute subcutaneous injection. Treatment order was randomized. Jugular blood was sampled for the measurement of prolactin, adrenocorticotropin (ACTH), and cortisol by radioimmunoassay.

RESULTS

Treatment with sertraline resulted in a comparable increase in prolactin secretion in male and female sheep. However, sertraline stimulated ACTH and cortisol secretion in females but not in males, a sexually dimorphic effect that was independent of circulating sex steroids. Treatment with imipramine had no effect on prolactin, ACTH or cortisol levels in male or female sheep.

CONCLUSIONS

These data suggest that the HPA axes of females are more sensitive to the stimulatory effects of serotonin following acute treatment with the SSRI, sertraline.