Reduction in the latency of action of antidepressants by 17 beta-estradiol in the forced swimming test.
BACKGROUND
Antidepressants (ADs) are slow to produce their therapeutic effect. This long latency promotes the development of new strategies to short their onset of action. Previous reports indicated that 17beta-estradiol (E(2)) promotes the antidepressant-like activity of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST).


OBJECTIVE
The aim of the present work was to analyze if E(2) reduces the antidepressant-like onset of action of venlafaxine (VLX), FLX, and DMI.


METHODS
Independent groups of ovariectomized female Wistar rats were tested in the FST and in the open field after chronic (1 to 14 days) treatment with VLX (20 mg/kg/day), FLX (1.25 mg/kg/day), or DMI (1.25 mg/kg/day) alone or in combination with a single injection of E(2) (2.5 microg/rat sc, 8 h before FST).


RESULTS
VLX, FLX, or DMI by themselves at these doses did not induce changes in the FST at short intervals after their injection (from 1 to 7 days). The addition of E(2) promoted the antidepressant-like effect of VLX and DMI as early as day 1. Such action was also evident after 3, for FLX, and 14 days for both FLX and DMI, but not for VLX. The behavioral actions of these ADs combined with E(2) were not accompanied by increases in general activity in the open-field test.


CONCLUSIONS
E(2) clearly reduced the latency to the onset of action for these ADs in the FST. These results represent an interesting therapeutic strategy for the treatment of depression in perimenopausal women.
Estrada-Camarena
E
E
Farmacología Conductual Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México City, Mexico.
Rivera
N M Vega
NM
Berlanga
C
C
Fernández-Guasti
A
A
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003511:Cyclohexanols / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007279:Injections, Subcutaneous; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013550:Swimming / Q000502:physiology / Q000523:psychology*; D000069470:Venlafaxine Hydrochloride
D018759:Adrenergic Uptake Inhibitors; D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003891:Desipramine; D004958:Estradiol; D004967:Estrogens; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride
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