Interaction of desipramine with steroid hormones on experimental anxiety

The present study analyzes if estradiol benzoate and/or progesterone interact with desmethylimipramine (DMI) to diminish experimental anxiety. The animal model of anxiety used was the conditioned defensive burying test. Dose response curves for DMI (0.625, 1.25 and 2.5 mg/kg, every 24 h, during 21 days), estradiol benzoate (0.5, 1.0, 2.0 and 4.0 micrograms/rat, 48 h) and progesterone (0.5, 1.0 and 2.0 mg/rat, -4 h) were made in ovariectomized rats. DMI per se decreased dose dependently the cumulative burying time, an effect considered as anxiolytic-like. Progesterone produced a decrease in burying at the highest dose, while estradiol benzoate had no effect on defensive burying. Both, progesterone (0.5 mg/rat) and estradiol benzoate (4.0 micrograms/rat) were able to decrease the cumulative burying behavior when injected with a subthreshold dose of DMI (1.25 mg/kg). In addition, the effect of DMI (1.25 mg/kg) plus the combination of estradiol benzoate and progesterone, sequentially administered (48 h and 4 h before the tests, respectively), also produced a synergistic decrease in burying behavior. In general, the treatments produced no changes in burying behavior latency, neither in spontaneous ambulation or in nociception. It is concluded that DMI synergizes its anxiolytic-like effect when administered with estradiol alone or in combination with progesterone. Present data provide experimental evidence suggesting an interaction between hormones and antidepressants. Results are discussed on the basis of the interaction between steroids and serotonergic or GABAergic receptors.