Interaction of desipramine with steroid hormones on experimental anxiety

The present study analyzes if estradiol benzoate and/or progesterone intera ct with desmethylimipramine (DMI) to diminish experimental anxiety. The ani mal 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 d ays), estradiol benzoate (0.5, 1.0, 2.0 and 4.0 mu g/rat, 48 h) and progest erone (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 c onsidered as anxiolytic-like. Progesterone produced a decrease in burying a t the highest dose, while estradiol benzoate had no effect on defensive bur ying. Both: progesterone (0.5 mg/rat) and estradiol benzoate (4.0 mu g/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 (1.2 5 mg/kg) plus the combination of estradiol benzoate and progesterone, seque ntially administered (48 h and 4 h before the tests, respectively), also pr oduced a synergistic decrease in burying behavior. In general, the treatmen ts produced no changes in burying behavior latency, neither in spontaneous ambulation or in nociception. It is concluded that DMI synergizes its anxio lytic-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 serotonegic or GABAergic receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.