Research Paper Volume 14, Issue 22 pp 9210—9220
Resident intruder paradigm-induced PMDD rat model of premenstrual irritability: behavioral phenotypes, drug intervention, and biomarkers
- 1 Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 2 Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 3 College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 4 Marxism College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 5 School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
Received: August 10, 2022 Accepted: November 16, 2022 Published: November 27, 2022
https://doi.org/10.18632/aging.204402How to Cite
Copyright: © 2022 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Premenstrual dysphoric disorder (PMDD) is high in women of childbearing age with obvious premenstrual irritability. However, reliable animal models are still lacking.
Materials and Methods: PMDD rat model of premenstrual irritability was induced by the resident-intruder paradigm (RIP). Behavioral characteristics were determined by the aggressive behavior test, elevated plus maze, open-field test, and breast width measurement. The estrous cycle in rats was artificially manipulated by bilateral ovariectomy and exogenous hormone injection to verify the model phenotype’s dependence on the estrous cycle.
Fluoxetine and Baixiangdan capsules were administered by gavage to determine the symptom improvement effect of PMDD irritability. Biomarkers in serum and brain were detected using ELISA, and GABRA4 was detected in the brain by RT-PCR and Western blot.
Results: Rat models demonstrated similar clinical characteristics as PMDD, such as premenstrual irritability and anxiety, and the above symptoms were estrous cycle-dependent. In addition, the levels of progesterone (P) and ALLO hormones decreased in the serum, hippocampus, amygdala, and frontal lobe in the NR phase. The contents of 5-HT in the brain were significantly increased, while NE and GABA contents were considerably reduced. Moreover, mRNA and protein expression of GABRA4 levels in model rats’ amygdala, hippocampus, and frontal lobe were significantly increased, while drug intervention downregulated its expression in these tissues.
Conclusion: Premenstrual irritability rat model of PMDD demonstrates a behavioral phenotype consistent with the clinical symptoms of PMDD and micro index. The increased levels of 5-HT, NE, and expression of GABRA4, as well as the decrease of GABA, P, and ALLO levels, may be critical biomarkers of the abnormal changes that occur during the pathogenesis of PMDD.