Authors: Dhir, Ashish; Kulkarni, S.K.

Source: Canadian Journal of Physiology and Pharmacology, Volume 86, Number 10, October 2008 , pp. 726-735(10)

Publisher: NRC Research Press

Abstract:

17β-estradiol has been reported to possess antidepressant-like activity in animal models of depression, although the mechanism for its effect is not well understood. The present study is an effort in this direction to explore the mechanism of the antidepressant-like effect of 17β-estradiol in a mouse model(s) of behavioral depression (despair behavior). Despair behavior, expressed as helplessness to escape from a situation (immobility period), as in a forced swim test in which the animals are forced to swim for a total of 6 min, was recorded. The antiimmobility effects (antidepressant-like) of 17β-estradiol were compared with those of standard drugs like venlafaxine (16 mg/kg, i.p.). 17β-estradiol produced a U-shaped effect in decreasing the immobility period. It had no effect on locomotor activity of the animal. The antidepressant-like effect was comparable to that of venlafaxine (16 mg/kg, i.p.). 17β-estradiol also exhibited a similar profile of antidepressant action in the tail suspension test. When coadministered with other antidepressant drugs, 17β-estradiol (5 μg/kg, i.p.) potentiated the antiimmobility effect of subeffective doses of fluoxetine (5 mg/kg, i.p.), venlafaxine (2 mg/kg, i.p.), or bupropion (10 mg/kg, i.p.), but not of desipramine (5 mg/kg, i.p.) or tranylcypromine (2 mg/kg, i.p.), in the forced swim test. The reduction in the immobility period elicited by 17β-estradiol (20 μg/kg, i.p.) was reversed by haloperidol (0.5 mg/kg, i.p.; a D₂ dopamine receptor antagonist), SCH 23390 (0.5 mg/kg, i.p.; a D₁ dopamine receptor antagonist), and sulpiride (5 mg/kg, i.p.; a specific dopamine D₂ receptor antagonist). In mice pretreated with (+)-pentazocine (2.5 mg/kg, i.p.; a high-affinity sigma-1 receptor agonist), 17β-estradiol (5 μg/kg, i.p.) produced a synergistic effect. In contrast, pretreatment with progesterone (10 mg/kg, s.c.; a sigma-1 receptor antagonist neurosteroid), rimcazole (5 mg/kg, i.p.; another sigma-1 receptor antagonist), or BD 1047 (1 mg/kg, i.p.; a novel sigma-1 receptor antagonist) reversed the antiimmobility effects of 17β-estradiol (20 μg/kg, i.p.). Similarly, in mice pretreated with a subthreshold dose of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A serotonin receptor agonist), 17β-estradiol (5 μg/kg, i.p.) produced an antidepressant-like effect. These findings demonstrate that 17β-estradiol exerted an antidepressant-like effect preferentially through the modulation of dopaminergic and serotonergic receptors. This action may also involve the participation of sigma-1 receptors.

Des études ont indiqué que le 17β-œstradiol possède une activité de type antidépressif dans les modèles animaux de dépression, bien que le mécanisme de cet effet soit mal connu. La présente étude propose d'examiner le mécanisme de l'effet de type antidépressif du 17β-œstradiol dans un ou des modèles de souris de dépression comportementale (comportement de désespoirl). Le comportement de désespoir, exprimé comme l'impuissance à se sortir d'une situation (période d'immobilité), comme dans le test de la nage forcée après que les animaux ont été forcés de nager pendant une période de 6 min, a été enregistré. Les effets antiimmobilité (de type antidépressif) du 17β-œstradiol ont été comparés avec ceux de médicaments standards comme la venlafaxine (16 mg/kg, i.p.). Le 17β-œstradiol a provoqué un effet en U en diminuant la période d'immobilité. Il n'a pas eu d'effet sur l'action locomotrice de l'animal.

Document Type: Research article

Publication date: 2008-10-01

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