Pubertal exposure to anabolic androgenic steroids increases spine densities on neurons in the limbic system of male rats

Abstract

Human studies show that the number of teenagers abusing anabolic androgenic steroids (AAS) is increasing. During adolescence, brain development is altered by androgen exposure, which suggests that AAS may potentially alter central nervous system development. The goal of the present study was to determine whether pubertal AAS exposure increased dendritic spine densities on neurons within the medial amygdala and the dorsal hippocampus. Pubertal gonadally intact male rats received the AAS testosterone propionate (5mg/kg) or vehicle for 5 days/week for four weeks. To determine the long-term implications of pubertal AAS use, another set of males received the same AAS treatment and were then withdrawn from AAS exposure for 4 weeks. Results showed that pubertal AAS exposure significantly increased spine densities on neurons in the anterior medial amygdala, posterodorsal medial amygdala, and the CA1 region of the hippocampus compared to gonadally intact control males. Spine densities returned to control levels within the anterior medial amygdala and the posterodorsal medial amygdala 4 weeks after withdrawal. However, spine densities remained significantly elevated after AAS withdrawal in the CA1 region of the hippocampus, suggesting that pubertal AAS exposure may have a long-lasting impact on CA1 hippocampal neuroanatomy. Since pubertal AAS exposure increased spine densities and most excitatory synapses in the central nervous system occur on dendritic spines, AAS may increase neuronal excitation. It is proposed that this increase in excitation may underlie the behavioral responses seen in pubertal AAS-treated male rats. KeywordsTestosterone; Medial Amygdala; Hippocampus; Withdrawal; DiI Anabolic androgenic steroid (AAS) use by human adolescent males is on the rise (Burnett and Kleiman, 1994, DuRant et al., 1995, Melia et al., 1996. This is of particular concern because puberty is a time when increasing endogenous hormone levels influence brain maturation (Primus and Kellogg, 1990, Sisk et al., 2003), which may be adversely affected by AAS exposure. 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 the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 November 15. Two brain regions that have been found to be sensitive to pubertal hormones in both human and animal studies are the hippocampus and amygdala (Meyer et al., 1978, Giedd et al., 1996a, Giedd et al., 1996b, Romeo and Sisk, 2001, Giedd et al., 2006, Zehr et al., 2006. The volume of the amygdala and hippocampus has been shown to increase with age in human adolescents (Giedd et al., 1...

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