Monoamine transporters show decreased uptake with delta and kappa opioid receptors

James G. Lamp ¹*, Benjamin J. Menarchek ¹*, Allison N. White ², and Vincent S. Setola ^1,2
1Department of Neuroscience and ²Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Morgantown, WV 26506

Presentation No.: 9

Assigned Category (Presentation Format): Biological & Health Sciences (Oral Presentations)

Student’s Major: Neuroscience

Such neuropsychiatric illnesses as depression, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder are treated using medications targeting monoamine transporter (MAT) activity. However, these treatments are not always effective. In such cases, alternative/adjunctive therapies are used. Previous studies revealed a relationship between the kappa opioid receptor (KOR) and the dopamine transporter (DAT), but the relationship between other opioid receptors (ORs) and MATs has not been thoroughly characterized. Thus, cells expressing one of the three MATs in the absence or presence of one of the three ORs were treated with either vehicle or an appropriate OR agonist, and MAT activity was subsequently assessed. Our data suggest that coexpression of the delta OR (DOR) or KOR—but not the mu OR (MOR)—along with a MAT markedly decreases transporter-mediated substrate uptake. Additionally, the effects of ORs on MATs were insensitive to either OR agonist or pertussis toxin, a compound that deactivates OR-mediated G protein signaling. These findings suggest that KORs and DORs each have antidepressant-like effects on MATs, suggesting that these receptors may be targets for new antidepressants.

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: WVU's SURE program (Rita Rio & Michelle Richards-Babb)