Research Report Adolescent anabolic androgenic steroids reorganize the glutamatergic neural circuitry in the hypothalamus Maria Carrillo, Lesley A. Ricci, Richard H. Melloni Jr ⁎ Behavioral Neuroscience Program, Department of Psychology, 125 Nightingale Hall, Northeastern University, 360 Huntington Avenue, Boston, MA 02155, USA ARTICLE INFO ABSTRACT Article history: Accepted 14 October 2008 Available online 5 November 2008 Chronic treatment with anabolic–androgenic steroids (AAS) during adolescence alters the activity of various neurotransmitter systems in male Syrian hamsters (Mesocricetus auratus). The present study was conducted to determine whether glutamatergic cells in the lateral anterior hypothalamus (LAH), a sub-region of the anterior hypothalamus, have lasting activation following adolescent AAS exposure, and to examine AAS-induced alterations in the connections between the LAH and the ventrolateral hypothalamus (VLH) governed by glutamate. Hamsters were administered AAS during adolescence and then examined for changes in FOS (protein product of the immediate early gene c-fos) and phosphate activated glutaminase (PAG; the rate-limiting enzyme in the synthesis of glutamate) immunoreactivity (FOS/PAG-IR) using double-label immunohistochemistry. In a second experiment, a retrograde tracing study was conducted using a red fluorescent tracer microinjected into the VLH. Then brains were processes for PAG immunofluorescence and examined for AAS-induced changes in the number of PAG positive cells containing the tracer (PAG/Tracer) in the LAH. When compared to oil-treated controls, AAS-treated hamsters showed significant increases in PAG-IR and FOS/PAG-IR in the LAH, decreases in afferent innervation from the LAH to the VLH and decreases in the total number of glutamate cells in the LAH projecting to the VLH. Together with previous research from our lab showing increased AAS-induced expression of PAG in the AH and increased glutamate receptor expression in the VLH, the current results suggest that adolescent AAS exposure leads to alterations in the function and expression of the glutamatergic system as well as changes in hypothalamic neural connections. In addition, the current results further strengthen the notion that a specific nucleus in the AH, the LAH is a critical hypothalamic sub-region particularly sensitive to AAS-induced neurodevelopmental effects. © 2008 Published by Elsevier B.V. Keywords: Adolescent AAS AH PAG Neutral connection VLH 1. Introduction Testosterone and its synthetic derivates, collectively termed anabolic–androgenic steroids (AAS), have the ability to alter normal cell function, protein synthesis and neurotransmis- sion (Foradori et al., 2008; Holterhus et al., 2002). In our laboratory we have used Syrian hamsters (Mesocricetus auratus) to investigate these neural modifications as they BRAIN RESEARCH 1249 (2009) 118 – 127 ⁎ Corresponding author. Fax: +1 617 373 8714. E-mail address: melloni@research.neu.edu (R.H. Melloni). 0006-8993/$ – see front matter © 2008 Published by Elsevier B.V. doi:10.1016/j.brainres.2008.10.053 available at www.sciencedirect.com www.elsevier.com/locate/brainres