Graduate Studies Faculty

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Major Areas 

Neuropharmacology; neuroendocrinology of ethanol intake and withdrawal 

Summary of Current Research 

Several research projects focus on the physiological significance of neuroactive steroid action. These endogenous modulators alter brain function by enhancing GABAergic neurotransmission via potent and selective interactions with GABA-A receptors. In a broad sense, studies are investigating whether drugs or physiological states which produce alterations in endogenous allopregnanolone (ALLO) levels, the most potent neuroactive steroid, could influence seizure susceptibility, anxiety levels, drug withdrawal hyperexcitability or dysphoria, or patterns of drug intake and the response to drug intake.  One project is testing the hypothesis that a decrease in endogenous ALLO levels, which alters GABAergic tone, in conjunction with a decrease in GABA-A receptor sensitivity, contribute to the increased ethanol withdrawal severity in the selectively bred Withdrawal Seizure-Prone mice.  Long term goals of this research are to gain information that will aid in our understanding of the mechanisms underlying ethanol withdrawal as well as the therapeutic potential of neurosteroid treatment during ethanol withdrawal.  A second project is utilizing microinjection into discrete brain regions to identify the site(s) of action of ALLO to alter ethanol self-administration and reinstatement in male and female mice. One long term goal of this research is to evaluate the influence of neurosteroids on gender differences in human patterns of alcohol intake and the response to alcohol, since males and females differ in endogenous neurosteroid levels.  Two additional projects are using a combination of environmental and genetic manipulations to generate animal models of high alcohol intake.  The third project is pursuing a model whereby chronic intermittent alcohol vapor exposure and withdrawal produces high alcohol intake (termed "withdrawal-induced drinking" or WID).  The goal of these studies is to identify pertinent neurotransmitters and begin to discern neural sites that are important for the expression of WID.  A fourth project is examining the relationship between binge drinking and stress in adolescent and adult mice on subsequent ethanol intake.  These studies are testing the hypothesis that adaptations in glutamate neuroplasticity following binge drinking confer susceptibility for enhanced alcohol intake in adolescent mice during adulthood and that stress produces additional adaptations that bestow further vulnerability for increased alcohol consumption.  The goal of these studies is to gain information that can guide the development of new pharmacological strategies that can be used to reduce binge consumption and the transition to dependence.

Education 

B.S. (1978) Loyola Marymount University
Ph.D. (1989) University of Southern California 

Previous Positions 

NINDS Postdoctoral Research Fellow, University of California, Irvine