Ovariectomy-Induced Increases in Hypothalamic Serotonin-1A Receptor Function in Rats Are Prevented by Estradiol

Raap, D. K.; DonCarlos, Lydia L.; García, Francisca; Zhang, Yahong; Muma, Nancy A.; Battaglia, George; Kar, Louis D. Van de

doi:10.1159/000067582

Cited by 20 publications

(9 citation statements)

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“…In this sense, in ovariectomized Flinders rats (a genetic model of depression), the characteristic increased mRNA expression of 5-HT 1A receptors in some limbic areas such as amygdala, hypothalamus, and hippocampus, is reduced by a single injection of E 2 (Ö sterlund et al, 1999). Furthermore, in Wistar female rats, ovariectomy induces an increase in the sensitivity of 5-HT 1A receptors in the hypothalamus that is abolished by E 2 treatment (Raap et al, 2002). Taken together, these results support the notion that the actions of E 2 on 5-HT 1A receptors may promote adaptive changes Estrogens and 5-HT 1A receptors in the FST E Estrada-Camarena et al similar to those induced by antidepressants to exert their effects.…”

Section: Discussionsupporting

confidence: 73%

Participation of the 5-HT1A Receptor in the Antidepressant-Like Effect of Estrogens in the Forced Swimming Test

Estrada‐Camarena

Fernández‐Guasti

López‐Rubalcava

2005

Neuropsychopharmacol

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The aim of the present study was to explore the possible participation of the 5-HT 1A receptor in the antidepressant-like action of two estrogenic compounds: 17b-estradiol (E 2 ) and ethynil-estradiol (EE 2 ) in the FST. Ovariectomized female Wistar rats were used in all experiments. As a positive control, the effect of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n)-propil-aminotetraline (8-OH-DPAT; 0.0625, 0.125, 0.25 and 0.5 mg/kg) alone or in combination with WAY 100635 (0.5 and 1.0 mg/kg) was analyzed in the FST. In order to analyze the participation of the 5-HT 1A receptor in the antidepressant-like actions of estrogens, the effect of the selective antagonist WAY 100635 (0.5 and 1.0 mg/kg) in combination with E 2 (10 mg/rat) and EE 2 (5 mg/rat) was studied in the FST. In this case, WAY 100635 was administered either simultaneously with the estrogens (48 h before the FST test) or 30 min before the FST. On the other hand, a suboptimal dose of 8-OH-DPAT (0.0625 mg/kg), combined with a noneffective dose of E 2 (2.5 mg/rat) or EE 2 (1.25 mg/rat), was tested in the FST. The results showed that 8-OH-DPAT (0.25 and 0.5 mg/kg), E 2 (10 mg/rat), and EE 2 (5 mg/rat), by themselves, exerted an antidepressant-like action. The antagonist to the 5-HT 1A receptor WAY 100635, when applied together with 8-OH-DPAT or E 2 , blocked their antidepressant-like actions, but not the one induced by EE 2 . Interestingly, when the antagonist was applied 30 min before the FST, it was able to cancel the actions of EE 2 on immobility behavior, and had no effect on the actions of E 2. Finally, when a subthreshold dose of 8-OH-DPAT was combined with a noneffective dose of either E 2 or EE 2 , an antidepressant-like action was observed. The results support the notion that the 5-HT 1A receptor is one of the mediators of the antidepressant-like action of E 2 , and could indirectly contribute to the one induced by EE 2 .

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Section: Discussionsupporting

confidence: 73%

Participation of the 5-HT1A Receptor in the Antidepressant-Like Effect of Estrogens in the Forced Swimming Test

Estrada‐Camarena

Fernández‐Guasti

López‐Rubalcava

2005

Neuropsychopharmacol

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“…This lack of effect of estrogen suggests that estrogen does not reduce the expression of Gα z in the CRH neurons in the hypothalamic PVN, as also suggested by a previous study [60]. Hence, a possible reduction of Gα z proteins in oxytocin cells of the PVN may be masked by lack of reduction in the levels of Gα z in CRH neurons of this nucleus.…”

Section: Discussionsupporting

confidence: 62%

Estrogen Reduces Serotonin-1A Receptor-Mediated Oxytocin Release and Gα<sub>i/o/z</sub> Proteins in the Hypothalamus of Ovariectomized Rats

D’Souza¹,

Zhang²,

Damjanoska³

et al. 2004

Neuroendocrinology

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The present study examined the effect of estradiol on hypothalamic serotonin-1A (5-HT_1A) receptor signaling in female rats. We first examined the time-course effects of a single injection of the 5-HT_1A receptor agonist (±)8-OH-DPAT (5, 15 or 30 min prior to decapitation), and dose response of (+)8-OH-DPAT (50, 100, 200 or 500 µg/kg, s.c.) on plasma hormones in ovariectomized rats that received a daily injection of β-estradiol 3-benzoate (10 µg/day, s.c.) or vehicle (sesame oil) for 2 days. In vehicle- and estrogen-treated rats, the peak response of hormones occurred at 15 min after injection and the time-course of oxytocin and adrenocorticotropic hormone (ACTH) responses to an injection of 8-OH-DPAT were comparable. However, only the oxytocin response was reduced by estrogen treatment. A second experiment compared the ACTH and oxytocin responses with doses of 50 or 200 µg/kg, s.c. of (+)8-OH-DPAT vs. (±)8-OH-DPAT in ovariectomized rats that were treated with oil or β-estradiol 3-benzoate (10 µg/day, s.c.) for 2 days. (+)8-OH-DPAT and (±)8-OH-DPAT produced a similar magnitude of increase in plasma levels of ACTH and oxytocin. Treatment with β-estradiol 3-benzoate produced a significant and comparable reduction in the oxytocin response to the highest dose (200 µg/kg, s.c.) of both (+)8-OH-DPAT and (±)8-OH-DPAT but did not alter the ACTH response to either (+)8-OH-DPAT or (±)8-OH-DPAT. In the dose-response experiment, a dose of 50 µg/kg of (+)8-OH-DPAT produced a maximal increase in plasma levels of ACTH, while the maximal oxytocin response was achieved with a dose of 200 µg/kg, s.c. Treatment with β-estradiol 3-benzoate reduced the maximal oxytocin response to (+)8-OH-DPAT (by 29%) but did not alter the ACTH response to any doses of (+)8-OH-DPAT. To examine potential mechanisms mediating the effects of estrogen on 5-HT_1A receptor signaling, we measured the levels of Gα_i, Gα_oand Gα_zproteins, which couple 5-HT_1A receptors to their effector enzymes, in two subregions of the hypothalamus. The levels of Gα_z protein were reduced in the mediobasal hypothalamus (containing the ventromedial and arcuate nuclei), which mainly expresses estrogen receptor-α, but not in the paraventricular hypothalamus, which mainly expresses estrogen receptor-β. Estradiol reduced the levels of Gα_i2 and Gα_i3proteins in both hypothalamic regions but did not affect Gα_i1 levels in either area. Combined, the data suggest that racemic and stereoselective 8-OH-DPAT have similar neuroendocrine effects and that both estrogen receptor-α and estrogen receptor-β mediate the reduction in levels of Gα_i2,3 proteins.

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“…However, evaluation of E2 in this study is difficult, since intact females were used and the periods of their estrous cycle were not determined. Increased expression of 5-HT 1A receptors have been observed in prefrontal cortex and DRN of suicide victims with major depression (Arango et al 1995;Stockmeier et al 1998), and ER are known to decrease both 5-HT 1A receptor mRNA levels in the DRN of OVX monkeys (Pecins-Thompson and Bethea 1998), 5-HT 1A function in hippocampus and frontal cortex in OVX rats (Mize et al 2001), and 5-HT 1A signaling in the hypothalamus of OVX rats (Raap et al 2002). It is possible that the lack of E2 antidepressant-like effect observed here in BERKO mice was due to the E2 dose used, which was insufficient to overcome upregulation of 5-HT 1A receptors in the mutants.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice

et al. 2005

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Ovariectomy-Induced Increases in Hypothalamic Serotonin-1A Receptor Function in Rats Are Prevented by Estradiol

Cited by 20 publications

References 60 publications

Participation of the 5-HT1A Receptor in the Antidepressant-Like Effect of Estrogens in the Forced Swimming Test

Participation of the 5-HT1A Receptor in the Antidepressant-Like Effect of Estrogens in the Forced Swimming Test

Estrogen Reduces Serotonin-1A Receptor-Mediated Oxytocin Release and Gα<sub>i/o/z</sub> Proteins in the Hypothalamus of Ovariectomized Rats

17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice

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