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Leslie Morrow, PhD, and her lab recently published their research on the deleterious interaction between the neurosteroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) and the mu-opioid system activation during forced swim stress in rats in the journal of Biomolecules. In a previous study, Dr. Morrow and her lab observed that 3α,5α-THP down-regulation of HPA axis activity during stress is sex-, brain region-, and stressor-dependent. The team observed a deleterious submersion behavior in response to 3α,5α-THP (15 mg/kg) during forced swim stress that led them to investigate how 3α,5α-THP might affect behavioral coping strategies engaged in by the animal. Dr. Morrow and her lab investigated the synergic effects of 3α,5α-THP/opiate system activation in this behavior, provided the well-established involvement of the opioid system in HPA axis activation and its interaction with GABAergic neurosteroids. The results suggest that 3α,5α-THP has a deleterious effect combined with forced swim stress, which together induced an exacerbation of the opioid system, resulting in submersion behavior. The study is the first to demonstrate a possible deleterious behavior due to interaction between 3α,5α-THP and the opioid system in the context of forced swim stress. These findings call for future direct investigation of 3α,5α-THP and opiate interactions. The results may be important for enhancing the understanding of limitations of 3α,5α-THP in the treatment of neuropsychiatric disease and the development of new treatments for patients with neuropsychiatric disorders that involve HPA axis activation. The study can be accessed at

Boero G, McFarland MH, Tyler RE, O’Buckley TK, Chéry SL, Robinson DL, Besheer J, Morrow AL. Deleterious Interaction between the Neurosteroid (3α,5α)3-Hydroxypregnan-20-One (3α,5α-THP) and the Mu-Opioid System Activation during Forced Swim Stress in Rats. Biomolecules. 2023; 13(8):1205.