Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats
Stress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus–pituitary–adrenal (HPA) axis and impairments in the GABAA receptors’ benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate proges...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7259 |
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| author | Dannia Islas-Preciado Gabriela Ugalde-Fuentes Isabel Sollozo-Dupont María Eva González Trujano Nancy Cervantes-Anaya Erika Estrada-Camarena Carolina López-Rubalcava |
| author_facet | Dannia Islas-Preciado Gabriela Ugalde-Fuentes Isabel Sollozo-Dupont María Eva González Trujano Nancy Cervantes-Anaya Erika Estrada-Camarena Carolina López-Rubalcava |
| author_sort | Dannia Islas-Preciado |
| collection | DOAJ |
| description | Stress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus–pituitary–adrenal (HPA) axis and impairments in the GABAA receptors’ benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate progesterone withdrawal (PW) effects on anxiety, HPA axis response, and to explore indicators of GABAA functionality in the BDZ site. For five days, ovariectomized WKY rats were administered 2.0 mg/kg of progesterone. Twenty-four hours after the last administration, rats were tested in the anxiety-like burying behavior test (BBT) or elevated plus maze test (EPM), and corticosterone was determined. [3H]Flunitrazepam binding autoradiography served as the BDZ binding site index of the GABAA receptor in amygdala nuclei and hippocampus’s dentate gyrus (DG). Finally, different doses of diazepam in PW-WKY rats were tested in the BBT. PW induced anxiety-like behaviors in both BBT and EPM compared with No-PW rats. PW increased corticosterone, but was blunted when combined with PW and BBT. PW increased [3H]Flunitrazepam binding in the DG and central amygdala compared with No-PW rats. Diazepam at a low dose induced an anxiogenic-like response in PW rats, suggesting a paradoxical response to benzodiazepines. Overall, PW induced anxiety-like behavior, a blunted HPA axis response, and higher GABAAR/BZD binding site sensitivity in a stress-vulnerable rat strain. These findings demonstrate the role of stress-susceptibility in GABAAR functionality in a preclinical approximation of PMDD. |
| first_indexed | 2024-03-09T21:48:36Z |
| format | Article |
| id | doaj.art-0c41cc989a944e33ad4723156bbe9c3b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:36Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0c41cc989a944e33ad4723156bbe9c3b2023-11-23T20:10:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313725910.3390/ijms23137259Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto RatsDannia Islas-Preciado0Gabriela Ugalde-Fuentes1Isabel Sollozo-Dupont2María Eva González Trujano3Nancy Cervantes-Anaya4Erika Estrada-Camarena5Carolina López-Rubalcava6Lab de Neuropsicofarmacología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, MexicoLab de Neuropsicofarmacología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, MexicoLab de Neuropsicofarmacología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, MexicoLab de Neurofarmacología de Productos Naturales, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, MexicoLab de Neuropsicofarmacología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, MexicoLab de Neuropsicofarmacología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, MexicoDepartamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados IPN (Cinvestav-IPN), Ciudad de México 07360, MexicoStress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus–pituitary–adrenal (HPA) axis and impairments in the GABAA receptors’ benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate progesterone withdrawal (PW) effects on anxiety, HPA axis response, and to explore indicators of GABAA functionality in the BDZ site. For five days, ovariectomized WKY rats were administered 2.0 mg/kg of progesterone. Twenty-four hours after the last administration, rats were tested in the anxiety-like burying behavior test (BBT) or elevated plus maze test (EPM), and corticosterone was determined. [3H]Flunitrazepam binding autoradiography served as the BDZ binding site index of the GABAA receptor in amygdala nuclei and hippocampus’s dentate gyrus (DG). Finally, different doses of diazepam in PW-WKY rats were tested in the BBT. PW induced anxiety-like behaviors in both BBT and EPM compared with No-PW rats. PW increased corticosterone, but was blunted when combined with PW and BBT. PW increased [3H]Flunitrazepam binding in the DG and central amygdala compared with No-PW rats. Diazepam at a low dose induced an anxiogenic-like response in PW rats, suggesting a paradoxical response to benzodiazepines. Overall, PW induced anxiety-like behavior, a blunted HPA axis response, and higher GABAAR/BZD binding site sensitivity in a stress-vulnerable rat strain. These findings demonstrate the role of stress-susceptibility in GABAAR functionality in a preclinical approximation of PMDD.https://www.mdpi.com/1422-0067/23/13/7259anxiety-like behaviorprogesterone withdrawalBDZ site in the GABAA receptorHPA axis function |
| spellingShingle | Dannia Islas-Preciado Gabriela Ugalde-Fuentes Isabel Sollozo-Dupont María Eva González Trujano Nancy Cervantes-Anaya Erika Estrada-Camarena Carolina López-Rubalcava Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats International Journal of Molecular Sciences anxiety-like behavior progesterone withdrawal BDZ site in the GABAA receptor HPA axis function |
| title | Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats |
| title_full | Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats |
| title_fullStr | Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats |
| title_full_unstemmed | Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats |
| title_short | Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats |
| title_sort | anxiety like behavior and gabaar bdz binding site response to progesterone withdrawal in a stress vulnerable strain the wistar kyoto rats |
| topic | anxiety-like behavior progesterone withdrawal BDZ site in the GABAA receptor HPA axis function |
| url | https://www.mdpi.com/1422-0067/23/13/7259 |
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