Enhanced fear responses in mice treated with anabolic androgenic steroids.
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.
Agis-Balboa
Roberto Carlos
RC
The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Pibiri
Fabio
F
Nelson
Marianela
M
Pinna
Graziano
G
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D045930:Anabolic Agents / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D011280:Pregnanolone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*; D043343:Testosterone Propionate / Q000494:pharmacology*
D045930:Anabolic Agents; D000728:Androgens; D012333:RNA, Messenger; D013256:Steroids; D005473:Fluoxetine; D018698:Glutamic Acid; D011280:Pregnanolone; D015096:3-Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C036139:norfluoxetine; D043343:Testosterone Propionate