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... read moreof central 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
- Component ID:
- tufts:25446
- To Cite:
- DCA Citation Guide EndNote
