Jonathan Cueto-Escobedo1, Javier Andrade-Soto2, Monica Lima-Maximino3, Caio Maximino4, Fabiola Hernández-López5, Juan Francisco Rodríguez-Landa6. 1. Departamento de Investigación Clínica y Traslacional, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, Mexico. 2. Facultad de Química Farmacéutica Biológica, Universidad Veracruzana, Xalapa, Veracruz, Mexico. 3. Laboratório de Neurofarmacologia e Biofísica, Departamento de Morfologia e Ciências Fisiológicas, Universidade do Estado do Pará, Campus VIII, Marabá, Pará, Brazil. 4. Laboratório de Neurociências e Comportamento, Faculdade de Psicologia, Instituto de Estudos em Saúde e Biológicas, Universidade Federal do Sul e Sudeste do Pará, Marabá, Pará, Brazil. 5. Unidad de Medicina Familiar No. 66, Instituto Mexicano del Seguro Social (IMSS), Xalapa, Veracruz, Mexico. 6. Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Facultad de Química Farmacéutica Biológica, Universidad Veracruzana, Xalapa, Veracruz, Mexico. Electronic address: juarodriguez@uv.mx.
Abstract
RATIONALE: The absence of ovarian hormones that is characteristic of natural and surgical postmenopause in women is frequently related to such disorders as depression and anxiety. Chronic treatment with the flavonoid chrysin was previously shown to exert antidepressant-like effects in rodents subjected to validate behavioral models. Chrysin has also been shown to have anxiolytic-like properties, but its antidepressant-like effects and mechanism of action in the absence of ovarian hormones remain unknown. OBJECTIVES: To compare the effects of the flavonoid chrysin with the effects of the neurosteroids progesterone and allopregnanolone on depression-like behavior in ovariectomized rats and evaluate the participation of γ-aminobutyric acid-A (GABAA) receptors in these actions. METHODS: Ovariectomized female Wistar rats were subjected to the locomotor activity test and forced swim test. The animals were assigned to eight treatment groups: vehicle, chrysin (1 mg/kg), progesterone (1 mg/kg), allopregnanolone (1 mg/kg), bicuculline (1 mg/kg), and pretreatment with bicuculline followed by chrysin, progesterone or allopregnanolone, respectively. After the treatments, the rats underwent the behavioral tests. RESULTS: Chrysin, progesterone, and allopregnanolone increased the latency to the first immobility and decreased the total immobility time in the forced swim test. The number of crossings and the time spent rearing and grooming decreased from the pretest to test sessions in the locomotor activity test. Chrysin, progesterone, and allopregnanolone only prevented the decreases in rearing and grooming. Bicuculline blocked the effects of chrysin, progesterone, and allopregnanolone in both behavioral tests. CONCLUSIONS: These results show that the GABA-binding site at GABAA receptors participates in the acute antidepressant-like effects of chrysin, similar to neurosteroids, in ovariectomized rats.
RATIONALE: The absence of ovarian hormones that is characteristic of natural and surgical postmenopause in women is frequently related to such disorders as depression and anxiety. Chronic treatment with the flavonoidchrysin was previously shown to exert antidepressant-like effects in rodents subjected to validate behavioral models. Chrysin has also been shown to have anxiolytic-like properties, but its antidepressant-like effects and mechanism of action in the absence of ovarian hormones remain unknown. OBJECTIVES: To compare the effects of the flavonoidchrysin with the effects of the neurosteroids progesterone and allopregnanolone on depression-like behavior in ovariectomized rats and evaluate the participation of γ-aminobutyric acid-A (GABAA) receptors in these actions. METHODS: Ovariectomized female Wistar rats were subjected to the locomotor activity test and forced swim test. The animals were assigned to eight treatment groups: vehicle, chrysin (1 mg/kg), progesterone (1 mg/kg), allopregnanolone (1 mg/kg), bicuculline (1 mg/kg), and pretreatment with bicuculline followed by chrysin, progesterone or allopregnanolone, respectively. After the treatments, the rats underwent the behavioral tests. RESULTS:Chrysin, progesterone, and allopregnanolone increased the latency to the first immobility and decreased the total immobility time in the forced swim test. The number of crossings and the time spent rearing and grooming decreased from the pretest to test sessions in the locomotor activity test. Chrysin, progesterone, and allopregnanolone only prevented the decreases in rearing and grooming. Bicuculline blocked the effects of chrysin, progesterone, and allopregnanolone in both behavioral tests. CONCLUSIONS: These results show that the GABA-binding site at GABAA receptors participates in the acute antidepressant-like effects of chrysin, similar to neurosteroids, in ovariectomized rats.
Authors: Juan Francisco Rodríguez-Landa; León Jesús German-Ponciano; Abraham Puga-Olguín; Oscar Jerónimo Olmos-Vázquez Journal: Molecules Date: 2022-05-31 Impact factor: 4.927