Testosterone and nucleus accumbens dopamine in the male Syrian hamster

Abstract

SummaryMost drugs of abuse increase dopamine (DA) in nucleus accumbens (Acb). However, the effects of anabolic androgenic steroids (AAS) on Acb DA have not been examined. We determined the effects of subcutaneous (sc) testosterone (T) on Acb DA in male hamsters. The effects of sc amphetamine were also examined for comparison. In addition, Acb DA was evaluated during intracerebroventricular (ICV) T infusion, designed to mimic T intake during ICV T selfadministration in drug-naïve and drug-preexposed animals. Acb DA was measured using in vivo microdialysis and HPLC-EC. T (7.5 or 37.5 mg/kg), amphetamine (1 or 5 mg/kg), or vehicle was injected sc and Acb DA monitored for 4 hrs. In the ICV experiment, T (1 or 2 μg/infusion) or vehicle was infused ICV every 6 min for 4 hrs and Acb DA monitored. ICV T preexposure was accomplished by repeating the same ICV T infusion (1 μg/infusion) daily for 14 days, and T infusion was accompanied by microdialysis on 15 th day. Neither sc nor ICV T administration increased Acb DA. At high dose (2 μg/infusion), ICV T decreased Acb DA. Likewise, daily ICV infusion of T for 15 days did not alter Acb DA. In contrast, sc amphetamine significantly increased Acb DA at both doses. Therefore, unlike many drugs of abuse, AAS does not increase Acb DA levels. The reduction in DA at high T doses is likely due to autonomic depressant effects of AAS. We suggest that AAS act via mechanism distinct from those of stimulants, but may share neural substrates with other drugs of abuse. Keywordsanabolic androgenic steroid; testosterone; amphetamine; hamster; nucleus accumbens; dopamine; microdialysis; HPLC-EC; intracerebroventricular; subcutaneous Androgenic anabolic steroid (AAS) use is widespread among athletes and non-athletes (Yesalis et al., 1993). Physical (Leshner, 2000) and psychological (Brower, 2002;Pope and Katz, 1994) effects of AAS use are of significant concern from a public health perspective. Brower (2002) has recently suggested that most AAS users initiate use for the anabolic properties, but many subsequently develop physical and psychological dependence. However, the addictive potential of AAS has received little attention so far. The results of studies using animal models of drug abuse indicate that AAS are reinforcing. For example, AAS induces conditioned place preference (CPP) in rats (Packard et al., 1997) and mice (Arnedo et al., 2000). In addition, AAS *Address all reprint requests and correspondence to: Ruth I. Wood, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 1333 San Pablo St. BMT 401, Los Angeles, CA 90033, Telephone (323) 442-1980, Fax: (323) 442-3466, e-mail: riw@usc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during ...

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