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Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen
Theses and Dissertations
Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …
Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade
Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade
Theses and Dissertations
Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …