Related Experiment Video
Updated: Jun 24, 2026
Modified Fear Conditioning for Inducing Flight Behaviors in Mice
Published on: December 15, 2023
Enhanced fear responses in mice treated with anabolic androgenic steroids
Roberto Carlos Agis-Balboa1, Fabio Pibiri, Marianela Nelson
1The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Abstract:
Corticolimbic neurons express neurosteroid biosynthesis, which is altered during anabolic androgenic steroid (AAS) treatment. The brain circuits and neurons that underlie the behavioral deficits found after AAS treatment remain undefined. We studied the effects of testosterone propionate (testosterone) on fear conditioning responses and in primary output corticolimbic neurons on 5alpha-reductase-type-I and 3alpha-hydroxysteroid-dehydrogenase expression. Testosterone fails to change cued fear responses although it induces excessive contextual fear associated with corticolimbic 5alpha-reductase-type-I mRNA expression downregulation in the prefrontal cortex, hippocampus, and basolateral amygdala glutamatergic neurons. Increased fear responses are abolished by normalizing corticolimbic allopregnanolone levels with allopregnanolone treatment (8 micromol/kg) or selective brain steroidogenic stimulants, including S-norfluoxetine (1.8 micromol/kg). Agents that increase corticolimbic allopregnanolone levels may be beneficial in treating AAS users.
Insights
Anabolic androgenic steroid (AAS) treatment alters brain neurosteroids, leading to excessive fear. Restoring allopregnanolone levels with treatments may help anabolic androgenic steroid users overcome these behavioral deficits.
Area of Science:
- Neuroscience
- Endocrinology
- Behavioral Science
Background:
- Neurosteroid biosynthesis in corticolimbic neurons is affected by anabolic androgenic steroid (AAS) use.
- The specific brain circuits and neuronal mechanisms behind AAS-induced behavioral deficits are not fully understood.
Purpose of the Study:
- To investigate the impact of testosterone propionate on fear conditioning and neurosteroid enzyme expression in corticolimbic neurons.
- To identify the role of 5alpha-reductase-type-I and 3alpha-hydroxysteroid-dehydrogenase in AAS-associated behavioral changes.
Main Methods:
- Examined fear conditioning responses in the context of testosterone treatment.
- Assessed the expression of 5alpha-reductase-type-I and 3alpha-hydroxysteroid-dehydrogenase mRNA in key brain regions.
- Utilized allopregnanolone treatment and selective brain steroidogenic stimulants to modulate neurosteroid levels.
Main Results:
- Testosterone did not alter cued fear responses but induced excessive contextual fear.
- AAS treatment led to the downregulation of 5alpha-reductase-type-I mRNA in prefrontal cortex, hippocampus, and basolateral amygdala glutamatergic neurons.
- Increased fear responses were reversed by normalizing allopregnanolone levels.
Conclusions:
- Testosterone-induced excessive contextual fear is linked to reduced corticolimbic 5alpha-reductase-type-I expression.
- Restoring allopregnanolone levels effectively mitigates AAS-associated fear deficits.
- Therapeutic strategies targeting corticolimbic allopregnanolone may benefit individuals with AAS use disorder.
