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- Title
Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats.
- Authors
Islas-Preciado, Dannia; Ugalde-Fuentes, Gabriela; Sollozo-Dupont, Isabel; González Trujano, María Eva; Cervantes-Anaya, Nancy; Estrada-Camarena, Erika; López-Rubalcava, Carolina
- Abstract
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.
- Subjects
LABORATORY rats; BINDING sites; ANXIETY; PROGESTERONE; HYPOTHALAMIC-pituitary-adrenal axis; BENZODIAZEPINE receptors; AMYGDALOID body
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 13, p7259
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23137259