Marilyn McGinnis

Professor of Pharmacology
Ph.D., University of California - Los Angeles

Office: 210-567-8205
Email: mcginnism@uthscsa.edu

Keywords

KEYWORDS

Research Summary

My current research focus is to investigate the effects of anabolic-androgenic steroids (AAS) on brain and behavior. Anabolic steroid use is on the rise, especially in adolescent males. Since increases in androgen levels are known to prodoundly influence the nervous system during adolescence, chronic exposure to high levels of androgens during pubertal development may produce enduring changes in brain maturation and subsequent behavioral expression. Using pubertal rats as the animal model, our laboratory has shown that exposure to AAS increases agression, and that this effect can be permanent. We demonstrated that AAS-induced aggression is not indiscriminate (i.e. 'roid rage). Current projects are aimed at determining the specific factors and conditions that predict whether or not aggression will be displayed in pubertal male rats exposed to AAS. For example, reports from the human literature suggested that males taking AAS were violent toward women. Using our animal model, we identified factors that contribute to aggression toward females by AAS-exposed males. We have also shown that males exposed to AAS are more likely to respond aggressively to provocation. Our laboratory has devised novel behavioral test procedures to identify the mechanisms underlying the increased aggression in response to provocation in male rats exposed to AAS. These data will be correlated with hormonal and neurochemical measures in brain.

Another area of active investigation is the role of serotonin in mediating increased aggression in AAS-treated males. Low serotonin has been associated with enhanced aggression and there is some evidence that testosterone lowers serotonin. Thus we are measuring brain serotonin in areas known to contain serotonin and/or androgen receptors. Specifically, we are using PCPA to lower serotonin and HPLC to measure 5HT and its major metabolites in frontal cortex, striatum, hippocampus, hypothalamus and brainstem. One intriguing finding thus far, is that males with low serotonin are very aggressive when exposed to AAS during puberty. This suggests that low serotonin may be a predictive factor in determining whether AAS use will potentiate aggression.

We are also interested in the effects of adolescent AAS exposure on brain development. Using DiI to label neurons and confocal microscopy combined with image analysis to quantify dendritic spines, we recently demonstrated that pubertal AAS exposure increases dendritic spine density in the amygdala and the hippocampus. Moreover, the increased spine density in the hippocampus remained even after AAS withdrawal. This is the first demonstration of a neuroanatomical change in the brain due to AAS exposure and supports the hypothesis that pubertal AAS exposure can affect brain maturation. We are currently investigating the effects of AAS on spine density in other brain regions.