Region‐ and domain‐dependent action of nomifensine. (26th April 2014)

• Record Type: Journal Article
• Authors: Shu, Zhan; Taylor, I. Mitch; Walters, Seth H.; Michael, Adrian C.
• Is Part Of: European journal of neuroscience. Volume 40:Number 2(2014:Jul.)
• Page Start: 2320
• Page End: 2328
• Publication Date: 2014-04-26
• Subjects: Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.12604
• Languages: English
• ISSNs: 0953-816X

Abstract

<abstract abstract-type="main" id="ejn12604-abs-0001"> <title>Abstract</title> <p>The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast‐scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain‐dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked DA overflow in the slow domains compared with the fast domains. To seek a kinetic explanation for nomifensine's selective actions, we quantified the apparent K_M of DA clearance by numerically evaluating the derivative of the descending phase of the DA signal after the end of the stimulus. For comparison, we likewise quantified the apparent K_M in the domains of the DS. As expected, because it is a competitive inhibitor, nomifensine significantly increased the apparent K_M in both the fast and slow domains of both the NAcc and DS. However, our analysis also led to the novel finding that nomifensine preferentially increases the apparent K_M in the NAcc compared with the DS; the apparent K_M increased by ~500% in the NAcc and by ~200% in the DS.</p> </abstract>