Region- and domain-dependent action of nomifensine

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Abstract

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 KM 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 KM in the domains of the DS. As expected, because it is a competitive inhibitor, nomifensine significantly increased the apparent KM 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 KM in the NAcc compared with the DS; the apparent KM increased by ˜500% in the NAcc and by ˜200% in the DS.

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. Our findings reveal that within the NAcc, nomifensine preferentially enhanced evoked dopamine overflow in the slow compared to the fast domains. Our analysis also leads to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared to the DS: apparent KM increased by ˜500% in the NAcc and ˜200% in the DS.

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