2020, Number 1
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Salud Mental 2020; 43 (1)
Actions of progesterone on depression-like behavior in a model of surgical menopause are mediated by GABAA receptors
Rodríguez-Landa JF, Olmos-Vázquez OJ, Dutra da CBP, Lima-Maximino M, Maximino C, Guillén-Ruiz G
Language: English
References: 79
Page: 43-53
PDF size: 773.43 Kb.
ABSTRACT
Introduction. In rats, long-term ovariectomy results in low concentrations of steroid hormones and reproduces
anxiety- and depression-like behavior after surgical menopause in women. Progesterone produces antidepressant-
like effects two weeks post-ovariectomy (i.e., early post-ovariectomy) through actions on γ-aminobutyric
acid-A (GABA
A) receptors, but its antidepressant-like effects and mechanism of action in rats eight weeks
post-ovariectomy (i.e., late post-ovariectomy, considered a model of surgical menopause) remain unknown.
Objective. To explore the antidepressant-like effects of progesterone and the participation of GABA
A receptors
in rats eight weeks post-ovariectomy.
Method. Long-term ovariectomized female Wistar rats were treated
sub-acutely with vehicle or progesterone (.5, 1, and 2 mg/kg) and subjected to the open field and forced swim
tests, and behavior was compared with cycling or fluoxetine-treated rats. The rats were then pretreated with
picrotoxin (1 mg/kg) followed by progesterone (1 mg/kg) to explore the role of GABA
A receptors in long-terminduced
depression-like behavior.
Results. Long-term ovariectomized rats exhibited depression-like behavior
in the forced swim test compared with intact rats, an effect that was not observed in progesterone- and fluoxetine-
treated long-term ovariectomized rats. These effects were not attributable to psychomotor alterations. In
the open field test, the time spent rearing and grooming was lower in ovariectomized rats compared with intact
rats, which was not observed in progesterone- and fluoxetine-treated rats. Picrotoxin blocked the effects of
progesterone in both behavioral tests.
Discussion and conclusion. These results indicated that sub-acute
progesterone treatment reduced depression-like behavior through actions on GABA
A receptors in a rat model
of surgical menopause.
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