The Placebo Effect in a Dish: Implications for Underlying Subcellular Mechanisms
Tanner, Heather.
2018
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Abstract: The placebo effect is well known as one of the founding premises for FDA-sanctioned clinical trials of new medications, yet there is very little scientific understanding of the cellular substrates of the phenomenon and lack of predictive biomarkers for the strength of the placebo response. Few prior correlative studies on the neurobiology of the placebo effect suggests the activation of ... read morecentral dopamine neurotransmission during a placebo response. The present project intends to identify the cellular and molecular mechanisms that are linked to the placebo effect in peripheral paracrine and central monoamine-secreting cells. We follow an innovative and unconventional approach in trying to induce neurotransmitter release as a response to an inert stimulus in primary dissociated cells in culture. At this first stage of our studies, we chose to conduct our experiments in rat adrenal chromaffin cells which are considered an excellent model of exocytosis for catecholamine-releasing neurons and at the same time are crucially involved at the systems level in setting the sympathetic tone and in disorders like the Cushing syndrome and hyperprolactinemia. We use the cutting-edge method of carbon fiber amperometry to assess catecholamine quantal release in real time in response to a high potassium stimulating solution in physiological temperature (37oC). Following two stimulations within 10 minutes, we expose each chromaffin cell to only a physiological temperature saline and assess release of catecholamine quanta by cells based on the prior association between the active secretagogue and physiological temperature. Cells are otherwise bathing in room temperature aCSF media. We predict that the cells predisposed to a placebo response will release catecholamine quanta when exposed to physiological temperature saline without the active secretagogue. We then proceed to identify differences in catecholamine kinetics and vesicular stores involved in the release of quanta from placebo prone cells versus non-responding cells. The above study represents the first effort to describe the molecular signature of the placebo effect in an animal and cellular model. The end overall objective of such an effort would be the development of a screening assay for human patients identifying biomarkers for the potential of a placebo therapy in advance.
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Pharmacology and Drug Development.
Advisor: Emmanuel Pothos.
Keywords: Pharmacology, and Neurosciences.read less - ID:
- kh04f2081
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