Alan Frazer, Ph.D.
Although recently retired, my line of research is continuing to be carried out by collaborators in the Department with my former lab members now working directly with them and my still being involved- but at a distance. My primary research interest has been the mechanism of action of antidepressant drugs. Historically, the focus of my lab was to study how chronic treatment of rats with antidepressants affects the functioning of two monoamine systems, noradrenergic and serotonergic, that are important targets for their clinical effects. More recently, interest in treatment refractory depression led us to study two treatments for it, vagal nerve stimulation or ketamine. These studies focused on both the mechanisms of action of these treatments and the circuits in brain necessary for their beneficial effects. The latter studies have been carried out in collaboration with Dr. Daniel Lodge in this Department, using state-of-the-art techniques such as optogenetics and designer receptors exclusively activated by designer drugs (DREADDs). A Research Assistant Professor in the Department, Dr. Flavia Carreno (pictured in Lab Members), has been the lead investigator for these studies. This work led us to study effects of selective negative allosteric modulators of α5-GABAA receptors. Such drugs were found to have antidepressant-like effects similar to those of ketamine but not having ketamine’s adverse effect profile. Finally, in collaboration with another faculty member, Dr. David Morilak, both cognitive and emotional behaviors in animal models of depression or PTSD have been studied and the effect that antidepressants have on such behaviors. A graduate student, Aleeza Stephens (pictured in Lab Members), led this work which is continuing under the direction of Dr. Morilak.
Related Diseases: major depressive disorder, post-traumatic stress disorder (PTSD)
Technniques: animal behavior, western blot analysis, stereotaxic surgery, optogenetics, chemogenetics (DREADDs)
- 1969 - PhD - Pharmacology - University of Pennsylvania
- 1964 - BS - Chemistry (Meritorious Honors) - Philadelphia College of Pharmacy and Science
- 9/1994 - Adjunct Professor - University of Pennsylvania School of Medicine, Pharmacology
- 9/1994 - Adjunct Professor - University of Texas at Austin College of Pharmacy
- 9/1993 - 03/2021 - Cross Faculty Appointment - The University of Texas Health Science Center at San Antonio, Psychiatry, San Antonio
- 9/1993 - 03/2021 - Chair and Professor - University of Texas Health Science Center, Pharmacology, San Antonio
- 07/2021 - Adjunct Professor of Pharmacology and Psychiatry - Perelman School of Medicine, University of Pennsylvania
Instruction & Training
- 1/2018 - Present, Membership on Supervising Committee, The University of Texas Health Science Center at San Antonio
- 5/2011 - Present, Membership on Supervising Committee, The University of Texas Health Science Center at San Antonio
- 2/2009 - 03/2021, Pre-Doctoral Student Supervision, The University of Texas Health Science Center at San Antonio
- 1/2002 - 03/2021, Post-Doctoral Student Supervision
Research & Grants
Funding Agency ASPET Title ASPET Fellowship Program for Undergraduate Students Status Active Period 6/2007 - Present Role Contributor Grant Detail
Funding Agency UTHSCSA President`s Translational and Entrepreneurial Research Fund Title Reducing the abuse liability of prescription opioids Status Active Period 1/2017 - 8/2017 Role Co-Principal Investigator Grant Detail
2 I01BX000559-08 (Frazer, PI) 3/14/2019-3/31/2023
VA Merit Award $316,570/yr
Selective negative allosteric modulators of alpha 5-GABAA receptors: novel psychotherapeutic drugs
This project tests the hypothesis that selective α5 negative allosteric modulators (NAMs) of GABAA receptors have the potential to be antidepressants without having the negative adverse effect profile of ketamine. The behavioral tests used to assess efficacy have relevance not only for depression but for PTSD as well. Experiments will be carried out in rats after their receiving mild electric foot-shock to induce behavioral deficits. Controls will not receive shock. Both male and female rats will be studied. The effect of the selective NAMs will be studied either after foot-shock (treatment) or before (prophylaxis). In addition, a chemogentic approach will be used to determine the pathways involved in specific behavioral effects of the selective NAM.