The Placebo Effect in a Dish: Implications for Underlying Subcellular Mechanisms
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 activatio... read moren of 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