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 https://www.mdpi.com/2218-273X/13/8/1205.
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. https://doi.org/10.3390/biom13081205