Abstract

MARTINEZ-MOTA, Lucía; HERRERA-PEREZ, José Jaime; OLIVARES NAZARIO, Maribel  and  FERNANDEZ-GUASTI, Alonso. Participation of gonadal hormones in the effect of antidepressant drugs in male rats. Salud Ment [online]. 2012, vol.35, n.5, pp.359-366. ISSN 0185-3325.

It has been proposed that gonadal hormones participate in regulation of mood and emotion in men as well as in the effect of psychoactive drugs, such as antidepressants. However, evaluation of this type of interactions has been poorly studied in clinic and basic studies. The objective of the present study was to determine the role of gonadal hormones, testosterone (T) and 17β-estradiol (E₂), one of its main metabolites, in the effect of two antidepressant drugs: desipramine and fluoxetine. The former is a tricyclic antidepressant that inhibits noradrenaline reuptake in a preferential manner, while the second is a serotonin selective reup-take inhibitor (SSRI) and the most prescribed antidepressant. Behavioral evaluations were conducted in adult male rats, intact or orchidectomized (Orx), treated with T (0-2 mg/rata), E₂ (0-40 µg/rata), desipramine (0-20 mg/kg), fluoxetine (0-20 mg/kg) and their combinations. Forced swimming test was used as an animal model to detect antidepressant-like effect induced by treatments, on the basis of its predictive validity. We found that desipramine and fluoxetine produced an anti-depressant-like effect in gonadally intact male rats. However, the antidepressant-like effect of both treatments was cancelled in Orx males. Treatment with E₂, but not with T, produced antidepressant-like actions in Orx males. Interestingly, treatment with E₂ restored the antidepressant-like effect of desipramine and fluoxetine, while supplementation with T only reestablished the antidepressant-like action of desipramine, evidencing that gonadal hormones have a differential participation in regulation of neurotransmitter systems involving in the antidepressant effect. In conclusion, the main testicular androgen T, participates in the expression of the effect of antidepressant drugs, mainly via conversion to its estrogenic metabolite E₂. These results give support to the idea that a combined therapy of gonadal hormones and antidepressant drugs may be more convenient to treat depressive disorders in hypogonadal men resistant to conventional antidepressant drugs.

Keywords : Animal models of depression; antidepressants; forced swimming test; estradiol; testosterone.

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