Assistant Professor
Schroeder Complex 429A
(414) 288-4534
E-mail
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 depression, generalized anxiety disorder, post-traumatic stress disorder and drug abuse.
One mechanism by which corticosteroids can alter behavioral and physiological processes is by modulating the actions of monoamine neurotransmitters (serotonin, dopamine, noradrenaline, adrenaline, and histamine). Organic cation transporter 3 (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 some of the effects of stress and glucocorticoids on monoaminergic neurotransmission. We use a variety of cellular, molecular, and behavioral tools to examine the role of OCT3 in regulation of extracellular concentrations of monoamines in specific brain regions, and to relate these effects to stress-related alterations in monoamine-dependent behaviors.
Gasser PJ, Orchinik M, Raju I, Lowry CA. (2009) Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain. J Comp Neurol 512 (4):529-555.
Lowry CA, Hale MW, Evans AK, Heerkens J, Staub D, Gasser PJ, Shekhar A. (2008) Serotonergic systems, anxiety, and affective disorders: focus on the dorsomedial part of the dorsal raphé 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 CA, Evans AK, Gasser PJ, Hale MW, Staub DR, Shekhar A. (2008) Topographic organization and chemarchitecture of the dorsal raphé nucleus and the median raphé nucleus. In "Serotonin and sleep: Molecular, Functional and Clinical Aspects” J Monti, S Pandi-Perumal, B Jacobs, D Nutt (Eds) Birkhauser Verlag AG, Basel, Switzerland.
Gasser PJ, Orchinik M. (2007) Vasopressin-induced translocation and proteolysis of protein kinaseCαin amphibian brain: modulation by corticosterone. Brain Res 1134 (1): 18-26.
Gasser PJ, Lowry CA, Orchink M. (2006) Corticosterone-sensitive monoamine transport in the rat dorsomedial hypothalamus: potential role for organic cation transporter 3 in stress-induced modulation of monoaminergic neurostransmission. J Neurosci, 26 (34): 8758-8766.
Orchinik M, Gasser PJ, Breuner CW. (2002) Rapid Corticosteroid Actions on Behavior: Cellular Mechanisms and Organismal Consequences. In "Hormones, Brain, and Behavior", D Pfaff (Ed) pp. 567-600. Academic Press, San Diego.
Orchinik M, Matthews L, Gasser PJ. (2000) Distinct specificity for corticosteroid binding sites in amphibian cytosol, neuronal membranes, and plasma. Gen Comp Endocrinol 118: 284-301.
Gasser PJ, Orchinik M. (2002) Membrane Glucocorticoid Receptors. In: "The Encyclopedia of Stress" G Fink (Ed) pp. 713-721. Academic Press, San Diego.
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