Poster abstracts

Poster number 83 submitted by Hua Wei

Residues in transmembrane domain 2 and 3 of mouse norepinephrine transporter contribute to high affinity recognition of cocaine, norepinephrine and antidepressants

Hua wei (pharmacology department, college of medicine), Howard H Gu (pharmacology department, college of medicine)

Abstract:
Cocaine inhibits dopamine (DAT), norepinephrine (NET) and serotonin (SERT)
transporters with high affinity, and evidence suggests a mechanistic role for all three of
these transporters in cocaine’s effects. Historically, research has focused on the dopamine
system but, studies have convincingly shown the norepinephrine system is also critical
for cocaine’s effects.Previously studies using mice lacking NET have suggested an
aversive role for the norepinephrine system in the effects of cocaine; however, there are
difficulties interpreting these results because of adaptive changes that may have occurred
during development due to the functional loss of NET. To better understand the role the
norepinephrine system in cocaine’s effects, we developed a functional NET with markedly
reduced affinity for cocaine (40-fold). We are in the process of generating a knock-in mouse
line bearing this mutated NET. We hope this mouse line will clarify the role of
norepinephrine in the effects of cocaine.

Keywords: cocaine, transporter, norepinephrine