Regulation of Extracellular Dopamine by the Norepinephrine Transporter
Article first published online: 13 NOV 2002
Journal of Neurochemistry
Volume 71, Issue 1, pages 274–280, July 1998
How to Cite
Yamamoto, B. K. and Novotney, S. (1998), Regulation of Extracellular Dopamine by the Norepinephrine Transporter. Journal of Neurochemistry, 71: 274–280. doi: 10.1046/j.1471-4159.1998.71010274.x
- Issue published online: 13 NOV 2002
- Article first published online: 13 NOV 2002
- Received January 8, 1998; revised manuscript received February 18, 1998; accepted February 19, 1998.
Abstract: There is growing evidence of an interaction between dopamine and norepinephrine. To test the hypothesis that norepinephrine terminals are involved in the uptake and removal of dopamine from the extracellular space, the norepinephrine uptake blocker desmethylimipramine (DMI) was infused locally while the extracellular concentrations of dopamine were simultaneously monitored. DMI increased the extracellular concentrations of dopamine in the medial prefrontal cortex and nucleus accumbens shell but had no effect in the striatum. The combined systemic administration of haloperidol and the local infusion of DMI produced an augmented increase in extracellular dopamine in the cortex compared with the increase produced by either drug alone. This synergistic increase in dopamine overflow is likely due to the combination of impulse-mediated dopamine release produced by haloperidol and blockade of the norepinephrine transporter. No such synergistic effects were observed in the nucleus accumbens and striatum. Local perfusion of the α2-antagonist idazoxan also increased the extracellular concentrations of dopamine in the cortex. Although the stimulation of extracellular dopamine by idazoxan and DMI could be due to the increased extracellular concentrations of norepinephrine produced by these drugs, an increase in dopamine also was observed in lesioned rats that were depleted of norepinephrine and challenged with haloperidol. This contrasted with the lack of an effect of haloperidol on cortical dopamine in unlesioned controls. These results suggest that norepinephrine terminals regulate extracellular dopamine concentrations in the medial prefrontal cortex and to a lesser extent in the nucleus accumbens shell through the uptake of dopamine by the norepinephrine transporter.