The prevalence of anabolic androgenic steroid (AAS) use has risen in teenagers and is now a major health problem. AAS use during adolescence is particularly alarming because puberty is a hormonally sensitive period during which adult behavioral patterns develop, and one consistent effect of AAS use is increased aggression. The goal of this research is to determine the factors underlying aggressive and impulsive behaviors in adolescent AAS users, employing rats as the animal model. The proposed studies will continue our work on AAS-exposed pubertal males.
Aim I will identify early experiential factors that predict whether aggression will be potentiated in AAS-treated males. The effects of early exposure to low serotonin and to social subjugation will be investigated. The effects of exposure to social subjugation on serotonin will be assessed.
Aim II will investigate the role of impulsivity in AAS-induced aggression.
The first aim will employ a test battery we have developed for measuring impulsivity in a sociosexual encounter. An advantage of this test is that it is biologically relevant and does not require extensive training or teaming. In the second experiment, the role of AAS in mediating impulsivity will be determined using the androgen receptor antagonist, hydroxyflutamide. In the third experiment, the role of serotonin in mediating impulsivity will be tested in AAS and gonadally intact rats using the SSRI, fluoxetine.
Aim III will investigate the long term effects of pubertal AAS exposure. The first experiment will identify long term effects of pubertal exposure to low brain serotonin in AAS-exposed males. The second experiment will determine whether increased aggressive behavior in socially subjugated males persists into adulthood.
In Aim I V we will assess the neuroanatomical effects of pubertal AAS exposure. Since gonadal hormones influence dendritic spine density, we will determine whether spine density is affected by AAS exposure during puberty. Spine densities in the medial amygdala and dorsal hippocampus will be quantified using the fluorescent dye, Dil. Disruption of the endogenous hormonal milieu during puberty may lead to irreversible behavioral and neurochemical consequences, and have a long-term negative impact on adult behavioral patterns. By superimposing AAS exposure on the developing nervous system, these studies will answer important questions regarding the effects of AAS use on the maturation of adolescent brain and aggressive behavior. ? ? ?

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Pilotte, Nancy S
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University of Texas Health Science Center San Antonio
Other Domestic Higher Education
San Antonio
United States
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Cunningham, Rebecca L; Lumia, Augustus R; McGinnis, Marilyn Y (2013) Androgenic anabolic steroid exposure during adolescence: ramifications for brain development and behavior. Horm Behav 64:350-6
Frahm, Krystle A; Lumia, Augustus R; Fernandez, Elizabeth et al. (2011) Effects of anabolic androgenic steroids and social subjugation on behavior and neurochemistry in male rats. Pharmacol Biochem Behav 97:416-22
Kubala, Kenneth H; McGinnis, Marilyn Y; Anderson, George M et al. (2008) The effects of an anabolic androgenic steroid and low serotonin on social and non-social behaviors in male rats. Brain Res 1232:21-9
Cunningham, R L; McGinnis, M Y (2008) Prepubertal social subjugation and anabolic androgenic steroid-induced aggression in male rats. J Neuroendocrinol 20:997-1005
McGinnis, Marilyn Y; Lumia, Augustus R; Tetel, Marc J et al. (2007) Effects of anabolic androgenic steroids on the development and expression of running wheel activity and circadian rhythms in male rats. Physiol Behav 92:1010-8
Cunningham, R L; Claiborne, B J; McGinnis, M Y (2007) Pubertal exposure to anabolic androgenic steroids increases spine densities on neurons in the limbic system of male rats. Neuroscience 150:609-15
Keleta, Yonas B; Lumia, Augustus R; Anderson, George M et al. (2007) Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin. Brain Res 1132:129-38
Cunningham, Rebecca L; McGinnis, Marilyn Y (2007) Factors influencing aggression toward females by male rats exposed to anabolic androgenic steroids during puberty. Horm Behav 51:135-41
Wesson, Daniel W; McGinnis, Marilyn Y (2006) Stacking anabolic androgenic steroids (AAS) during puberty in rats: a neuroendocrine and behavioral assessment. Pharmacol Biochem Behav 83:410-9
Cunningham, Rebecca L; McGinnis, Marilyn Y (2006) Physical provocation of pubertal anabolic androgenic steroid exposed male rats elicits aggression towards females. Horm Behav 50:410-6

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