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. Major depressive disorder (MDD) is a significant public health problem. The lifetime prevalence for MDD is estimated at about 16% which is equivalent to about 33 million U.S. adults with lifetime MDD. This is a disease that also takes lives - by suicide, which is the 11th leading cause of death in the U.S. The effectiveness of treatments for it, then, is of considerable importance. Although antidepressant drugs are effective, about 50% of patients do not achieve remission even after two trials with an antidepressant. Understanding the pharmacological effects of existing antidepressants better should aid in the development of medications with superior efficacy.
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. We measure both neurochemical and behavioral parameters and use techniques that permit neuroanatomical localization of drug effects. Such techniques include quantitative autoradiography, in vivo voltammetry and administration of drugs directly into specific sites in brain. Our recent projects include an examination of the effect of female sex steroids, namely estrogen and progesterone, on the ability of the most frequently prescribed class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), to alter the function of their primary cellular target which is 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. This study was carried out in collaboration with my long-time associate, Dr. Saloua Benmansour (pictured below).
Another current project carried out in collaboration with two other faculty in the Department of Pharmacology, Drs. T. Cunningham and S. Mifflin, examines brain areas activated by both acute and chronic vagal nerve stimulation (VNS) in the rat. VNS is now used for treatment-refractory depression but little is known about how it produces its beneficial clinical effects. We used immunohistochemistry for brain markers of either short-term (c-Fos) or long-term (Δ Fos B) neuronal activation to map regions in brain activated by either two hours or three weeks of VNS. Finally, in collaboration with another faculty member, Dr. D. Morilak, we are studying both cognitive and emotional behaviors in animal models of depression or PTSD and the effect that antidepressant treatments 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 secretary), the Collegium Internationale Neuro-Psychopharmacologicum, 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. In addition to serving on the editorial boards of several journals, he is currently the Editor-in-Chief of the International Journal of Neuropsychopharmacology.
Dr. Saloua Benmansour - Assistant Professor/Research
Dr. Flavia Carreno - Postdoctoral Fellow
Haifan Wu - PreDoctoral Fellow