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.
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
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.
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