TY  - GEN
N2  - Methamphetamine (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.
DO  - 10.6083/qf85nb81p
DO  - DOI
AB  - Methamphetamine (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.
T1  - The modulatory role of TAAR1 in neurotoxicity of  substituted amphetamines
DA  - 2019
AU  - Miner, Nicholas
L1  - https://digitalcollections.ohsu.edu/record/7479/files/nicholas.miner.2019.pdf
PB  - Oregon Health and Science University
PY  - 2019
ID  - 7479
L4  - https://digitalcollections.ohsu.edu/record/7479/files/nicholas.miner.2019.pdf
KW  - Neurotoxicity Syndromes
KW  - Dopamine
KW  - Methamphetamine
KW  - N-Methyl-3,4-methylenedioxyamphetamine
KW  - taar1 protein
KW  - vesicular monoamine transporter 2
TI  - The modulatory role of TAAR1 in neurotoxicity of  substituted amphetamines
Y1  - 2019
L2  - https://digitalcollections.ohsu.edu/record/7479/files/nicholas.miner.2019.pdf
LK  - https://digitalcollections.ohsu.edu/record/7479/files/nicholas.miner.2019.pdf
UR  - https://digitalcollections.ohsu.edu/record/7479/files/nicholas.miner.2019.pdf
ER  -