Stress leads, in all vertebrates, to the release of corticosteroid hormones from the adrenal glands. These hormones exert powerful neuromodulatory effects that lead to context- and state-dependent alterations in ongoing behavioral and physiological processes. The primary goals of my research are to identify mechanisms by which corticosteroids alter cognitive function, motivation, sensory processing, and neuroendocrine responses, leading to adaptive responses to acute stress; and to understand how these mechanisms may be involved in the pathophysiology of stress-related disorders including post-traumatic stress disorder, depression, and drug abuse. The hope is that this research will increase our understanding of the pathophysiology of stress-related neuropsychiatric disorders, and that it will lead to the development of novel, effective treatments for these disorders.
We use a combination of behavioral, molecular and biochemical techniques to examine the acute effects of glucocorticoids on cellular processes that may modulate behavior. Current studies focus on the role of organic cation transporter 3 (OCT3) in regulating monoamine clearance under basal and stress conditions. OCT3 is a high capacity transporter that mediates bidirectional transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine. OCT3-mediated transport is directly inhibited by corticosterone, suggesting a potential role for the transporter in mediating the effects of stress and glucocorticoids on monoaminergic neurotransmission. We have characterized the corticosterone sensitivity of OCT3 in acutely prepared brain tissue, and have described the distribution of the transporter throughout the rat brain. Current studies are focused on: a) the localization of OCT3 with respect to cellular markers of monoaminergic neurotransmission; b) the sensitivity of OCT3-mediated transport to various natural and synthetic corticosteroids; c) the role of OCT3 in regulating extracellular monoamine concentrations under basal and stimulated conditions; d) the role of OCT3 in stress-induced changes in behavior; and e) the effects of acute and chronic stress on expression and function of OCT3.
Selected Publications
- Hill, J.E., Shrestha, L., Makky, K., Hillard, C.J., Gasser, P.J. (submitted). Natural and synthetic corticosteroids inhibit uptake2-mediated transport in CNS neurons: role of organic cation transporter 3. Stress.
- Gasser, P.J., Orchinik, M., Raju, I., Lowry, C.A. (2009) Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain. J Comp Neurol. 512 (4): 529-555.
- Gasser, P.J., Lowry, C.A., Orchinik, M.. (2009). Acute corticosteroid action in the brain: mechanisms and implications. In: “Hormones, Brain, and Behavior” 2nd edition, D. Pfaff, A. Arnold, A. Etgen, S. Fahrbach, R. Rubin, eds. Academic Press, San Diego.
- Lowry, C.A., Hale, M.W., Evans, A.K., Heerkens, J., Staub, D., Gasser, P.J., Shekhar, A. (2008) Serotonergic systems, anxiety, and affective disorder: focus on the dorsomedial part of the dorsal raphe nucleus. In: “Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms” R. Kvetnansky, G. Aguilera, D. Goldstein, D. Jezova, O. Krizanova, E. Sabban, K. Pacek, eds. Ann. NY Acad. Sci. 1148: 86-94.
- Lowry, C.A., Evans, A.K., Gasser, P.J., Hale, M.W., Staub, D.R, Shekhar, A. (2008) Topographic organization and chemoarchitecture of dorsal raphe nucleus and the median raphe nucleus. In: “Serotonin and sleep: Molecular, Functional and Clinical Aspects”. Monti, J.M., Pandi-Perumal, S.R., Jacobs, B.L., Nutt, D.J. (Eds) Birkhauser Verlag AG, Basel, Switzerland.
- Gasser, P.J., Orchinik, M. (2007) Vasopressin-induced translocation and proteolysis of protein kinase Cα in an amphibian brain: modulation by corticosterone. Brain Res. 1134 (1):18-26.
- Gasser, P.J., Lowry, C.A., Orchinik, M. (2006) Corticosterone-sensitive monoamine transport in the rat dorsomedial hypothalamus: potential role for organic cation transporter 3 in stress-induced modulation of monoaminergic neurotransmission. J. Neurosci. 26 (34): 8758-8766.
- Orchinik, M., Matthews, L., Gasser, P.J. (2000) Distinct specificity for corticosteroid binding sites in amphibian cytosol, neuronal membranes, and plasma. Gen. Comp. Endocrinol. 118: 284-301.
Contact Biomedical Sciences
Department of Biomedical Sciences
College of Health Sciences
Schroeder Complex, 426
P.O. Box 1881
Milwaukee, WI 53201-1881
Phone: (414) 288-7251
Fax: (414) 288-6564
