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

PSYCHONEUROENDOCRINOLOGY

卷:91

Article

Mosher, Laura J.^1,2  Godar, Sean C.¹  Morissette, Marc³  McFarlin, Kenneth M.²  Scheggi, Simona^1,4  Gambarana, Carla⁴  Fowler, Stephen C.²  Di Paolo, Therese^3,5  Bortolato, Marco¹ 

[1] Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, LS Skaggs Hall,30 S 2000 E, Salt Lake City, UT 84112 USA

[2] Univ Kansas, Sch Pharm, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA

[3] Ctr Hosp Univ Quebec, CHUL, Neurosci Res Unit, Quebec City, PQ, Canada

[4] Univ Siena, Dept Mol & Dev Med, Siena, Italy

[5] Laval Univ, Fac Pharm, Quebec City, PQ, Canada

关键词: Transgenic mice;    Dominance;    Aggression;    Novelty seeking;    Risk taking;    Dopamine;    5 alpha-reductase;   

DOI  :  10.1016/j.psyneuen.2018.02.007

来源: Elsevier

【 摘 要 】

The enzyme steroid 5 alpha-reductase 2 (5 alpha R2) catalyzes the conversion of testosterone into the potent androgen 5 alpha-dihydrotestosterone. Previous investigations showed that 5 alpha R2 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 5 alpha R2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5 alpha R2 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 5 alpha R2 KO mice exhibited reduced D 2 -like dopamine receptor binding in the shell of the nucleus accumbens - a well-recognized molecular signature of social dominance. Collectively, these results suggest that 5 alpha R2 is involved in the establishment of social dominance and its behavioral manifestations. Further studies are warranted to understand how the metabolic actions of 5 alpha R2 on steroid profile may be implicated in social ranking, impulse control, and the modulation of dopamine receptor expression in the nucleus accumbens.

【 授权许可】

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