Steroid 5α-reductase 2 deficiency leads to reduced dominance-related and impulse-control behaviors.

TitleSteroid 5α-reductase 2 deficiency leads to reduced dominance-related and impulse-control behaviors.
Publication TypeJournal Article
Year of Publication2018
AuteursMosher, LJ, Godar, SC, Morissette, M, McFarlin, KM, Scheggi, S, Gambarana, C, Fowler, SC, Di Paolo, T, Bortolato, M
JournalPsychoneuroendocrinology
Volume91
Pagination95-104
Date Published2018 May
ISSN1873-3360
Abstract

The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses. Furthermore, male 5αR2 KO mice exhibited reduced D-like dopamine receptor binding in the shell of the nucleus accumbens - a well-recognized molecular signature of social dominance. Collectively, these results suggest that 5αR2 is involved in the establishment of social dominance and its behavioral manifestations. Further studies are warranted to understand how the metabolic actions of 5αR2 on steroid profile may be implicated in social ranking, impulse control, and the modulation of dopamine receptor expression in the nucleus accumbens.

DOI10.1016/j.psyneuen.2018.02.007
Alternate JournalPsychoneuroendocrinology
PubMed ID29544191
PubMed Central IDPMC5901899
Grant ListR01 MH104603 / MH / NIMH NIH HHS / United States
R21 HD070611 / HD / NICHD NIH HHS / United States