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Characterizing Opioid Receptor Modulation of Monoamine Transporters: A Potential Avenue for Treating Neuropsychiatric Diseases
Benjamin Menarchek
1*, James Lamp
1*, Allison White
1, and Vincent Setola
1,2
Departments of
1Neuroscience and
2Behavioral Medicine and Psychiatry, Rockefeller Neuroscience Institute
West Virginia University School of Medicine, Morgantown, WV 26506-9303
Presentation No.: 95
Assigned Category (Presentation Format): Neuroscience (Poster Presentations)
Student’s Major: Biology
Depression, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder are but a few neuropsychiatric conditions that can be alleviated by drugs that target monoamine transporters (MATs). MATs are responsible for the reuptake/clearance of serotonin, norepinephrine, and dopamine in the synaptic cleft. In the brain, MATs can be co-expressed with one or more of the three opioid receptors (KOR, DOR, and MOR). We sought to determine whether opioid receptor (OR) co-expression with MATs affects monoamine transporter activity. Cells expressing a MAT without an OR exhibited robust uptake of a fluorescent substrate; however, cells expressing a MAT with either KOR or DOR (but not MOR) displayed a marked decrease in substrate uptake. These data suggest that KOR and DOR each negatively affect MAT activity. Future experiments will investigate whether KOR and DOR affect MAT expression levels and whether KOR and/or DOR physically interact with MATs. These findings may shed light on the use of KOR- and/or DOR-targeting pharmaceuticals to treat neuropsychiatric illnesses involving MAT activity.
Funding: This work was funded in part by NIH/NIDA U18DA052497 (to VS) and NIH/NIDA R36DA051703 (to ANW). ANW acknowledges support from NIH/NIGMS T32GM132494.
Program/mechanism supporting research/creative efforts: Other
