Allopregnanolone Is Required for Prepulse Inhibition Deficits Induced by D1 Dopamine Receptor Activation

June 2019 in “ Psychoneuroendocrinology ”

Laura J. Mosher, Roberto Cadeddu, Sabrina Yen, Jeff Staudinger, Francesco Traccis, Stephen C. Fowler, Jamie Maguire, Marco Bortolato

allopregnanolone 5α-reductase type 1 D1 dopamine receptor GABA-A receptor PXR receptor AP 5αR1

Studysummary This study found that in rodent models, the ability of D1 dopamine receptor activation to impair sensory gating is facilitated by 5α-reductase type 1, which produces allopregnanolone. Our plain-language summary of this paper — not a Tressless recommendation.

The study demonstrated that the enzyme 5α-reductase type 1 (5αR1) was necessary for the prepulse inhibition (PPI) deficits induced by D1 dopamine receptor activation in mice. Knockout mice lacking 5αR1 were resistant to these deficits, which were restored by administering allopregnanolone (AP), but not other 5α-reduced steroids. The PPI-disrupting effects of the D1 receptor agonist were not influenced by GABA-A or PXR receptors, indicating that 5αR1 facilitates the negative impact of D1 receptor activation on information processing through the production of AP, independent of these receptors.

View this study on sciencedirect.com →

Discuss this study in the Community →

Research cited in this study

14 / 14 results

research Repurposing Steroidogenesis Inhibitors for the Therapy of Neuropsychiatric Disorders: Promises and Caveats

10 citations , May 2018 in “Neuropharmacology”

This study suggests that inhibitors of steroidogenic enzymes may have therapeutic potential for certain behavioral disorders linked to dopaminergic hyperfunction, despite concerns about their endocrine impacts.

research Steroid 5α-Reductase 2 Deficiency Leads to Reduced Dominance-Related and Impulse-Control Behaviors

14 citations , February 2018 in “Psychoneuroendocrinology”

This study found that male 5α-reductase 2 knockout mice showed deficits in social dominance behaviors and reduced dopamine receptor binding in a brain region related to social ranking.

research Allopregnanolone Mediates the Exacerbation of Tourette-Like Responses by Acute Stress in Mouse Models

25 citations , June 2017 in “Scientific reports”

This study suggests that stress may worsen Tourette syndrome symptoms in mice by increasing allopregnanolone synthesis, with findings supporting finasteride as a potential treatment to manage symptom fluctuations.

research The Neurosteroidogenic Enzyme 5α-Reductase Modulates the Role of D1 Dopamine Receptors in Rat Sensorimotor Gating

49 citations , September 2015 in “Psychoneuroendocrinology”

This study suggests that the 5α-reductase inhibitor finasteride modulates sensorimotor gating in rats by affecting D1 and D3 receptors, but not D2 receptors, with varying effects based on genetic strain.

research Adverse Effects of 5α-Reductase Inhibitors: What Do We Know, Don't Know, and Need to Know?

111 citations , August 2015 in “Reviews in Endocrine and Metabolic Disorders”

5α-reductase inhibitors may cause persistent sexual dysfunction and depression, needing more research on long-term effects.

research Inhibition Of 5α-Reductase Attenuates Behavioral Effects Of D1-, But Not D2-Like Receptor Agonists In C57BL/6 Mice

42 citations , August 2012 in “Psychoneuroendocrinology”

Finasteride reduces certain behaviors caused by D1-like receptor agonists but not by D2-like receptor agonists in mice.

research Inhibition of 5α-Reductase in the Nucleus Accumbens Counters Sensorimotor Gating Deficits Induced by Dopaminergic Activation

53 citations , October 2011 in “Psychoneuroendocrinology”

Finasteride may help improve certain brain function issues linked to dopamine.

A Preliminary Study of Finasteride in Tourette Syndrome

research MK-386, an Inhibitor of 5α-Reductase Type 1, Reduces Dihydrotestosterone Concentrations in Serum and Sebum Without Affecting Dihydrotestosterone Concentrations in Semen

37 citations , May 1997 in “The Journal of Clinical Endocrinology & Metabolism”

This study found that MK-386 selectively suppressed sebum DHT levels in a dose-dependent manner, suggesting potential use for treating acne.

research Four-Amino Acid Segment in Steroid 5 Alpha-Reductase 1 Confers Sensitivity to Finasteride, a Competitive Inhibitor

83 citations , April 1992 in “Journal of Biological Chemistry”

Four-amino acid part makes enzyme sensitive to finasteride.

Allopregnanolone Is Required for Prepulse Inhibition Deficits Induced by D1 Dopamine Receptor Activation

Research cited in this study

research Repurposing Steroidogenesis Inhibitors for the Therapy of Neuropsychiatric Disorders: Promises and Caveats

research Steroid 5α-Reductase 2 Deficiency Leads to Reduced Dominance-Related and Impulse-Control Behaviors

research Allopregnanolone Mediates the Exacerbation of Tourette-Like Responses by Acute Stress in Mouse Models

research The Neurosteroidogenic Enzyme 5α-Reductase Modulates the Role of D1 Dopamine Receptors in Rat Sensorimotor Gating

research Adverse Effects of 5α-Reductase Inhibitors: What Do We Know, Don't Know, and Need to Know?

research Inhibition Of 5α-Reductase Attenuates Behavioral Effects Of D1-, But Not D2-Like Receptor Agonists In C57BL/6 Mice

research Inhibition of 5α-Reductase in the Nucleus Accumbens Counters Sensorimotor Gating Deficits Induced by Dopaminergic Activation

research A Preliminary Study of Finasteride in Tourette Syndrome

research Steroid 5α-Reductase as a Novel Therapeutic Target for Schizophrenia and Other Neuropsychiatric Disorders

research Improvement of General Symptoms in a Chronic Psychotic Patient Treated with Finasteride: Case Report

research Antipsychotic-Like Properties of 5-Alpha-Reductase Inhibitors

research Treatment of Tourette’s Syndrome With Finasteride

research MK-386, an Inhibitor of 5α-Reductase Type 1, Reduces Dihydrotestosterone Concentrations in Serum and Sebum Without Affecting Dihydrotestosterone Concentrations in Semen

research Four-Amino Acid Segment in Steroid 5 Alpha-Reductase 1 Confers Sensitivity to Finasteride, a Competitive Inhibitor