000007479 001__ 7479
000007479 005__ 20231129124941.0
000007479 0247_ $$2DOI$$a10.6083/qf85nb81p
000007479 037__ $$aETD
000007479 245__ $$aThe modulatory role of TAAR1 in neurotoxicity of  substituted amphetamines
000007479 260__ $$bOregon Health and Science University
000007479 269__ $$a2019
000007479 336__ $$aDissertation
000007479 502__ $$bPh.D.
000007479 520__ $$aMethamphetamine (MA) use is a global epidemic, causing mental, physical, and societal damage. Although dopamine (DA) dysregulation is the hallmark of MA-induced neurotoxicity, many underlying mechanisms remain unknown. The trace amine-associated receptor 1 (TAAR1) is activated by numerous agonists, including MA and 3,4 methylenedioxymethamphetamine (MDMA). Activation of TAAR1 inhibits DA neuronal firing and decreases rewarding effects of amphetamines, suggesting TAAR1 mitigates their harmful effects. This dissertation investigated the regulatory role of TAAR1 on transitory and sustained neurotoxic effects of amphetamines in a mouse model. Neurotoxicity was assessed through quantification of striatal biomarkers indicative of DA terminal degeneration and astrocyte activation. Thermal response to amphetamines was also recorded as hyperthermia exacerbates neurotoxicity and hypothermia can provide neuroprotection.
000007479 542__ $$fIn copyright - single owner
000007479 650__ $$aNeurotoxicity Syndromes$$032271
000007479 650__ $$aDopamine$$018026
000007479 650__ $$aMethamphetamine$$022135
000007479 650__ $$aN-Methyl-3,4-methylenedioxyamphetamine$$031121
000007479 6531_ $$ataar1 protein
000007479 6531_ $$avesicular monoamine transporter 2
000007479 691__ $$aSchool of Medicine$$041369
000007479 692__ $$aDepartment of Behavioral Neuroscience$$041394
000007479 7001_ $$aMiner, Nicholas
000007479 8564_ $$964b6c887-4814-4ec7-ab20-37dc30eebfda$$s4304013$$uhttps://digitalcollections.ohsu.edu/record/7479/files/nicholas.miner.2019.pdf
000007479 905__ $$a/rest/prod/qf/85/nb/81/qf85nb81p
000007479 909CO $$ooai:digitalcollections.ohsu.edu:7479$$pstudent-work
000007479 980__ $$aTheses and Dissertations