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Hormones and Behavior
Volume 50, Issue 2, August 2006, Pages 216-222
 
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doi:10.1016/j.yhbeh.2006.03.003    How to Cite or Link Using DOI (Opens New Window)
Copyright © 2006 Elsevier Inc. All rights reserved.

Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats

Kassandra L. Edingerb and Cheryl A. Fryea, b, c, d, Corresponding Author Contact Information, E-mail The Corresponding Author

aDepartment of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA bDepartment of Biological Sciences, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA cCenters for Neuroscience, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA dLife Science Research, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA

Received 15 December 2005; 
revised 10 March 2006; 
accepted 11 March 2006. 
Available online 24 April 2006.

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Abstract

Testosterone (T) and its 5α-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5α-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts that were empty or contained flutamide were applied directly to the dorsal hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in the open field, elevated plus maze, or defensive freezing tasks. GDX rats exhibited significantly more anxiety-like behaviors than intact or DHT-replaced rats. Intact and DHT-replaced rats administered flutamide to the hippocampus showed significantly more anxiety-like behavior than did intact and DHT-replaced controls. However, flutamide alone did not increase anxiety-like behavior of GDX rats. Together, these findings suggest that androgens can decrease anxiety-like behavior of male rats in part through DHT's actions at androgen receptors in the hippocampus.

Keywords: Androgens; Testosterone; Flutamide; Androgen receptors; Dihydrotestosterone

Article Outline

Introduction
Methods
Animals and housing
Surgery and hormone replacement
Behavioral testing
Open field
Elevated plus maze
Defensive freezing task
Perfusion and histological analysis
Statistical analyses
Results
Open field
Elevated plus maze
Defensive freezing task
Discussion
Acknowledgements
References




Hormones and Behavior
Volume 50, Issue 2, August 2006, Pages 216-222
 
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