The abuse of androgenic-anabolic steroids (AAS) has increased dramatically amongst the adolescent population and represents a serious drug problem in the United States. The most consistently cited behavioral sequelae of AAS abuse is increased aggressive behavior. The arginine vasopressin (AVP) neural system has been strongly implicated in the regulation of aggressive behavior. It is hypothesized that abuse of anabolic steroids during the adolescent period of neural development results in increased aggressive behavior correlated with developmental changes in the AVP neural system. These changes may be a function of alterations in the expression of AVP and/or the expression and activity of specific AVP receptors. Alternatively, these developmental changes may be due to modifications in the synaptic connectivity of the AVP neural system. Studies outlined in this proposal will utilize an animal model to examine the behavioral and neurobiological effects of high dose AAS exposure during a period that is physiologically similar to adolescence in humans. The first set of experiments will determine whether exposure to AAS during adolescent development facilitates aggressive behavior in golden hamsters using the resident/intruder paradigm of offensive aggression. The next set of experiments will determine whether AAS exposure during adolescence alters the molecular biology and neurochemistry of the AVP neural system. These studies will employ the use of cDNA fragments, antibodies, and selective receptor ligands to visualize and quantitate the activity of the genes encoding AVP and the AVP V1A subtype receptor. The last set of experiments will determine whether exposure to AAS during adolescent development alters the synaptic connections of the AVP neural system. Changes in synaptic connectivity will be visualized and quantitated by wide-field digital microscopy and immunoelectron microscopy. The data obtained from these studies should provide valuable information regarding the increased risk of aggressive and violent behavior in those individuals who abuse AAS during early life, and the neurobiological sequelae of prolonged high dose use of AAS. This knowledge is important in helping us to identify developmental periods that are particularly vulnerable to environmental insult, and to document the neurobiological changes that may predispose individuals to behave in a self-destructive or violent manner later in life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DA010547-02
Application #
2661230
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Thadani, Pushpa
Project Start
1996-09-01
Project End
2001-06-30
Budget Start
1997-08-01
Budget End
1998-06-30
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Psychiatry
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Morrison, T R; Sikes, R W; Melloni Jr, R H (2016) Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus. Neuroscience 315:1-17
Morrison, Thomas R; Ricci, Lesley A; Melloni Jr, Richard H (2016) Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids. Horm Behav 86:55-63
Morrison, Thomas R; Ricci, Lesley A; Melloni Jr, Richard H (2015) Anabolic/androgenic steroid administration during adolescence and adulthood differentially modulates aggression and anxiety. Horm Behav 69:132-8
Ricci, Lesley A; Morrison, Thomas R; Melloni Jr, Richard H (2013) Adolescent anabolic/androgenic steroids: Aggression and anxiety during exposure predict behavioral responding during withdrawal in Syrian hamsters (Mesocricetus auratus). Horm Behav 64:770-80
Ricci, Lesley A; Morrison, Thomas R; Melloni Jr, Richard H (2012) Serotonin modulates anxiety-like behaviors during withdrawal from adolescent anabolic-androgenic steroid exposure in Syrian hamsters. Horm Behav 62:569-78
Carrillo, Maria; Ricci, Lesley A; Melloni, Richard H (2011) Developmental and withdrawal effects of adolescent AAS exposure on the glutamatergic system in hamsters. Behav Neurosci 125:452-64