--- title: Can a chemical reduce aggressive behavior during the late phase of a cycle similar to the menstrual cycle? description: In a rat study, a chemical called isoallopregnanolone reduced aggressive behavior during the late cycle phase. The treatment brought aggression down to levels url: https://niyora.com/research/papers/isoallopregnanolone-inhibits-estrus-cycle-dependent-aggressive-behavior-2023/ --- - [Niyora](https://niyora.com/) - [Research](https://niyora.com/research/) - [Library](https://niyora.com/research/library/) - Can a chemical reduce aggressive behavior during the late phase of a cycle similar to the menstrual cycle? Lab study, 2023 # Can a chemical reduce aggressive behavior during the late phase of a cycle similar to the menstrual cycle? In a rat study, a chemical called isoallopregnanolone reduced aggressive behavior during the late cycle phase. The treatment brought aggression down to levels seen in the early phase of the cycle. Early or limited evidence Female Wistar rats with naturally occurring cycle-dependent aggressive behavior ## What they did Researchers studied female Wistar rats, some of which naturally showed increased aggression during certain phases of their cycle. They gave some rats isoallopregnanolone while using a test where a rat was placed with another rat to measure aggression. They compared aggression levels in different cycle phases with and without the chemical. ## What they found 42% of rats showed higher aggression during the late phase of the cycle (diestrus) compared to the early phase (estrus). When given isoallopregnanolone, the extra aggression seen in the late phase was reduced by 89%, bringing aggression levels to match the early phase. ## What it means for you A chemical that affects the brain may help reduce cycle-related aggression in rats. Since this is animal research in laboratory conditions, it does not yet tell us whether the approach would work the same way in humans. The findings suggest a possible pathway for understanding and treating irritability in conditions like PMDD, but much more research is needed. 42% of rats showed cycle-dependent aggression 89% reduction in aggression with treatment ## About the study Original title Isoallopregnanolone Inhibits Estrus Cycle-Dependent Aggressive Behavior Authors Bäckström T, Bengtsson SKS, Sjöstedt J et al. Journal Biomolecules Year 2023 Study design Lab study What was tested Isoallopregnanolone chemical treatment Open access Yes Read the paper [doi.org/10.3390/biom13061017](https://doi.org/10.3390/biom13061017) Original abstract Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1β2γ2L and α4β3δ GABA-A receptor subtypes. In this study, we also investigated whether ISO could antagonize the estrus cycle-dependent aggressive behaviors in female Wistar rats using a resident-intruder test. Our results confirmed previous reports of estrus cycle-dependent behaviors in that 42% of the tested rats showed higher levels of irritability/aggression at diestrus compared to those at estrus. Furthermore, we found that, during the treatment with ISO, the aggressive behavior at diestrus was alleviated to a level comparable to that of estrus. We noticed an 89% reduction in the increase in aggressive behavior at diestrus compared to that at estrus. Vehicle treatment in the same animals showed a minimal effect on the diestrus-related aggressive behavior. In conclusion, we showed that ISO can antagonize Steroid-PAM both in α1β2γ2L and α4β3δ GABA-A receptor subtypes and inhibit estrus cycle-dependent aggressive behavior. Reproduced under CC-BY. ## Topics [Premenstrual dysphoric disorder (PMDD)](https://niyora.com/research/topics/condition-pmdd/)[Irritability and anger](https://niyora.com/research/topics/symptom-irritability-anger/)[Neurosteroids (allopregnanolone)](https://niyora.com/research/topics/treatment-neurosteroids/)[Pregnancy and postpartum](https://niyora.com/research/topics/comorbidity-postpartum/) Research tells you what helps on average. Niyora helps on the day it hits. Calm down, see it another way, and decide what to say, with a PMS and PMDD app built by a doctor. ## Related studies Review, 2003 How do menstrual cycle hormones affect the brain and cause mood disorders like PMDD? Randomised trial, 2021 Does sepranolone reduce PMDD symptoms? Randomised trial, 2021 Does blocking progesterone receptors help women with PMDD control anger and aggression? Randomised trial, 2017 Does Sepranolone reduce symptoms of severe premenstrual syndrome (PMDD)? Case-control study, 2026 What role do brain chemicals called neurosteroids play in PMDD? Lab study, 2023 How does allopregnanolone help with PMDD symptoms? Ask AI about this page Copy prompt ChatGPT ↗ Claude ↗ Perplexity ↗ Google AI Mode ↗ Grok ↗