Alan Frazer, Ph.D.
Professor of Pharmacology and Psychiatry
Chair of Pharmacology
Ph.D., University of Pennsylvania
antidepressants, norepinephrine, serotonin, transporters, vagal nerve stimulation
My primary research interest is the mechanism of action of antidepressant drugs. Historically, the focus of my lab has been 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. Both neurochemical and behavioral parameters are measured and techniques are used that permit neuroanatomical localization of drug effects. Our recent projects include an examination of the ability of female sex steroids, namely estrogen and progesterone, to inhibit the inhibitory effect of the most frequently prescribed class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), on their primary cellular target, namely the serotonin transporter. This is relevant as MDD is more common in females than in males and depressive episodes in women may be more recurrent, longer in length and associated with more functional impairment than those in men. These studies were carried out in collaboration with my long-time associate, Dr. Saloua Benmansour (pictured below).
Our interest in treatment refractory depression caused us to study two treatments for it. One, vagal nerve stimulation, is approved by the FDA whereas the other, ketamine, is more experimental. Our studies have focused on the receptor, TrkB, for brain derived neurotrophic factor (BDNF), particularly the ability of these treatments to activate it by phosphorylation and the signaling molecules linked to it. In collaboration with Dr. Daniel Lodge in this Department, we are studying the brain circuits involved in their effects using state-of-the-art techniques such as optogenetics and designer receptors exclusively activated by designer drugs (DREADDs). A postdoctoral fellow in my lab, Dr. Flavia Carreño (pictured below), has been the lead investigator for these studies. Finally, in collaboration with another faculty member, Dr. David Morilak, we are studying both cognitive and emotional behaviors in animal models of depression on PTSD and the effect that antidepressant treatments and behavioral therapies have on such behaviors.
Appointments, Boards, Committees and Memberships
Dr. Frazer is a member of numerous societies including the American Society of Pharmacology and Experimental Therapeutics, the American College of Neuropsychopharmacology (of which he is the President-Elect), the International College of Neuropsychopharmacology (CINP), of which he is a Councillor, and the Society of Neuroscience. He has been awarded a Merit Award from NIH and has been a Career Scientist of the Department of Veterans Affairs. He is currently the Editor-in-Chief of the International Journal of Neuropsychopharmacology, the official publication of the CINP.