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

ABSTRACT: The enzyme steroid 5?-reductase 2 (5?R2) catalyzes the conversion of testosterone into the potent androgen 5?-dihydrotestosterone. Previous investigations showed that 5?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?R2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5?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?R2 KO mice exhibited reduced D2-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?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?R2 on steroid profile may be implicated in social ranking, impulse control, and the modulation of dopamine receptor expression in the nucleus accumbens.

SUBMITTER: Mosher LJ

PROVIDER: S-EPMC5901899 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Mosher Laura J LJ Godar Sean C SC Morissette Marc M McFarlin Kenneth M KM Scheggi Simona S Gambarana Carla C Fowler Stephen C SC Di Paolo Thérèse T Bortolato Marco M

Psychoneuroendocrinology 20180216

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 ...[more]

PMID: 29544191

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Project description:BackgroundStress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied.MethodsThis study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients, and 37 demographically matched healthy controls were examined during brief individualized imagery trials of stress, alcohol cue, and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale.ResultsImpulse control difficulties in AUD patients were significantly associated with hypo-active response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p < 0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex compared to controls, which are core regions of emotion regulation, suggesting AUD patients' decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p < 0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p < 0.05, with adjusted Bonferroni correction).ConclusionsHypo-active response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism.

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

Publications

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

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