Research Projects

The long-term goals of my laboratory are to understand the cellular basis for behavioral changes associated with anabolic androgenic steroid (AAS) use. AAS are testosterone derivatives originally designed for clinical applications, but now predominantly illicitly self-administered at concentrations estimated to be 10-1000 times the levels of endogenous androgens. AAS use has steadily increased over the past few decades, and the profile of those who self-administer these steroids has been changing to include not only elite athletes, but also an increasing number of recreational users, including junior high and high school students. In addition to consequences for the function of peripheral organ systems, AAS use is also known to have significant effects on the brain and behavior, most notably on the expression of aggression, anxiety and sexual/reproductive behaviors. Our studies are focused on determining how the AAS alter neuronal excitability, classical neurotransmission (with a specific

emphasis on GABAA receptors) and neuromodulation (with a specific emphasis on corticotropin releasing factor) in regions of the mammalian hypothalamus and forebrain that are highly steroid-sensitive and provide the fundamental circuitry for those behaviors most commonly altered with AAS use. To this end, we use a number of different wild type, transgenic and mutant mouse strains to determine the effects of both acute and chronic exposure to AAS, integrating studies from the molecular to the whole animal level. Our approaches include patch clamp recording from brain slices and isolated primary neurons, real time RT-PRC analyses of specific brain regions and of single identified neurons, confocal immunohistochemistry, Western blot analysis, and behavioral measures of stress, anxiety and aggression. By these studies we hope to better understand the neuronal mechanisms that underlie the reported effects of AAS abuse on both reproductive competence and psychological states, particularly in adolescent users.