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Enhanced fear responses in mice treated with anabolic androgenic steroids

Agis-Balboa, Roberto Carlos; Pibiri, Fabio; Nelson, Marianela; Pinna, Graziano

doi: 10.1097/WNR.0b013e32832a2393
NEUROENDOCRINOLOGY

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 5α-reductase-type-I and 3α-hydroxysteroid-dehydrogenase expression. Testosterone fails to change cued fear responses although it induces excessive contextual fear associated with corticolimbic 5α-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 μmol/kg) or selective brain steroidogenic stimulants, including S-norfluoxetine (1.8 μmol/kg). Agents that increase corticolimbic allopregnanolone levels may be beneficial in treating AAS users.

The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

Correspondence to Professor Graziano Pinna, PhD, The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA

Tel: +1 312 355 1464; fax: +1 312 413 4569; e-mail: gpinna@psych.uic.edu

Present address of Roberto Carlos Agis-Balboa is European Neuroscience Institute Göttingen, Laboratory for Aging and Cognitive Diseases, University of Göttingen Medical School/Max Planck Society, Göttingen 37077, Germany

Received 13 January 2009 accepted 8 February 2009

© 2009 Lippincott Williams & Wilkins, Inc.