Functional screening of established and experimental weight loss drugs in terms of their effects on central dopamine release kinetics
Abstract: Obesity is
considered to be one of the main and important causes of morbidity, mortality, and
limited life quality. There are many reasons and theories explaining the mechanism
obesity and one of these theories is the brain Dopaminergic signaling pathway. It has
shown that dopamine plays a major role in obesity; it has revealed that obese subjects
have limited dopamine receptors whi... read morech in turn impair brain dopamine circuit and this
will lead the obese subject to eat more as a compensatory mechanism to overcome the
dopaminergic limitation. However, some anti-obesity medications work on the dopamine
pathway and correct this defect. In this study, we examine some medication such as
Topiramate and NAAA inhibitor to see if they have any role in reducing weight through
the dopaminergic system. We use electrophysiological methods to examine the dopamine
release from the brain striatum and compare it with the baseline release. At the end of
this study, Topiramate has shown a high reduction in the dopamine release when compared
with the baseline release. However, NAAA inhibitor showed the opposite. It has displayed
that NAAA inhibitor increase dopamine release comparing with the baseline dopamine
release. In conclusion, we are assuming that Topiramate reduces weight through a
different mechanism other than increasing dopamine level. In contrast, NAAA inhibitor
may show a reduction in weight through a different mechanism as well. Further
investigation is needed in order to understand the link between obesity and dopaminergic
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Pharmacology and Drug Development.
Advisor: Emmanuel Pothos.
Committee: Efi Kokkotou.
Keyword: Nanoscience.read less