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Effects of chronic anabolic androgenic steroid exposure on GABAergic neurotransmission and neuronal activity in the mamalian forebrain.

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Call No.	QP563.G32 P46 2008
Author	Penatti, Carlos Alberto Avellaneda.
Title	Effects of chronic anabolic androgenic steroid exposure on GABAergic neurotransmission and neuronal activity in the mamalian forebrain.
Date	2008
Abstract	Anabolic androgenic steroids (AAS) are derivatives of testosterone originally designed for therapeutic applications to enhance anabolic potency (protein synthesis and muscle growth) while exerting low androgenic (masculinizing) effects. The potential benefits of specific applications in clinical conditions are counterbalanced by the detrimental health effects of the same compounds in the drug abuse environment, such as the disruption of neuroendocrine axis and increase in impulsivity and aggression. In the sexually dimorphic brain, the chronic supraphysiological levels of AAS reported to be present in drug abusers may disrupt normal gonadal hormone signaling mediated by nuclear estrogen receptors (ER) and androgen receptors (AR) imparting aberrant effects on the organization and function of neurotransmitter systems and neuronal activity. Regions such as the medial preoptic area (mPOA) comprise several subsets of ER and AR-expressing neurons sensitive to AAS effects that are important for many aspects of neuroendocrine control and behavior. The action potential (AP) firing patterns of neurons in mPOA govern the overall level of activity within this important multi-modal forebrain region, which is characterized by complex neurocircuitry with various neurotransmitter systems. Among them, GABA (γ-aminobutyric acid) type A (GABA A ) receptors are pivotal for normal neurotransmission, and GABAergic transmission has a significant impact on mPOA-mediated processing that underlies the expression of aggression and the control of reproduction. The first goal of this work was to characterize chronic AAS-dependent effects in GABAergic neurotransmission and AP firing of mPOA neurons correlating the molecular and physiological alterations to aspects of behavior associated with AAS drug abuse in male and female mice. The second goal was to determine the relative involvement of ER and AR signaling pathways in mediating the AAS-induced changes in the brain and involvement in aggressive behavior using an AR-deficient male mouse model. Experiments described here provide neurobiological evidence that AAS taken as drugs of abuse will cause changes in GABA A receptor subunit expression and function and in overall neuronal activity within the mPOA that in turn, result in impairment of the regulatory mechanisms of the neuroendocrine axis and related aspects of animal behavior in male and females.
Description	xix, 253 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Leslie P. Henderson
Subject	GABA -- Receptors. Anabolic steroids -- Physiological effect. Androgens -- Physiological effect. Prosencephalon. Neurotransmitters -- Effect of drugs on. Psychoneuroendocrinology.
College	Dartmouth Medical School -- Department of Physiology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.192

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Effects of Chronic Anabolic Androgenic Steroid Exposure on GABAergic Neurotransmission and Neuronal Activity in the Mammalian Forebrain A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Physiology By Carlos Alberto Avellaneda Penatti DARTMOUTH COLLEGE Hanover, New Hampshire May, 2008 Examining Committee _______________________________ (chair) Dr. Leslie P. Henderson ______________________________ Dr. Ann S. Clark ______________________________ Dr. Eugene E. Nattie ______________________________ Dr. Valerie A. Galton ______________________________ Dr. Lori L. McMahon ____________________________ Charles K. Barlowe, PhD Dean of Graduate Studies

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