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Restricted diffusion of dopamine in the rat dorsal striatum.

ABSTRACT: Recent evidence has shown that the dorsal striatum of the rat is arranged as a patchwork of domains that exhibit distinct dopamine kinetics and concentrations. This raises the pressing question of how these distinct domains are maintained, especially if dopamine is able to diffuse through the extracellular space. Diffusion between the domains would eliminate the concentration differences and, thereby, the domains themselves. The present study is a closer examination of dopamine's ability to diffuse in the extracellular space. We used voltammetry to record dopamine overflow in dorsal striatum while stimulating the medial forebrain bundle over a range of stimulus currents and frequencies. We also examined the effects of drugs that modulated the dopamine release (raclopride and quinpirole) and uptake (nomifensine). Examining the details of the temporal features of the evoked profiles reveals no clear evidence for long-distance diffusion of dopamine between fast and slow domains, even though uptake inhibition by nomifensine clearly prolongs the time that dopamine resides in the extracellular space. Our observations support the conclusion that striatal tissue has the capacity to retain dopamine molecules, thereby limiting its tendency to diffuse through the extracellular space.

SUBMITTER: Taylor IM

PROVIDER: S-EPMC3656739 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Restricted diffusion of dopamine in the rat dorsal striatum.

Taylor I Mitch IM Ilitchev Alexandre I AI Michael Adrian C AC

ACS chemical neuroscience 20130503 5

Recent evidence has shown that the dorsal striatum of the rat is arranged as a patchwork of domains that exhibit distinct dopamine kinetics and concentrations. This raises the pressing question of how these distinct domains are maintained, especially if dopamine is able to diffuse through the extracellular space. Diffusion between the domains would eliminate the concentration differences and, thereby, the domains themselves. The present study is a closer examination of dopamine's ability to diff ...[more]

PMID: 23600442

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Project description:Dopamine (DA), a highly significant neurotransmitter in the mammalian central nervous system, operates on multiple time scales to affect a diverse array of physiological functions. The significance of DA in human health is heightened by its role in a variety of pathologies. Voltammetric measurements of electrically evoked DA release have brought to light the existence of a patchwork of DA kinetic domains in the dorsal striatum (DS) of the rat. Thus, it becomes necessary to consider how these domains might be related to specific aspects of DA's functions. Responses evoked in the fast and slow domains are distinct in both amplitude and temporal profile. Herein, we report that responses evoked in fast domains can be further classified into four distinct types, types 1-4. The DS, therefore, exhibits a total of at least five distinct evoked responses (four fast types and one slow type). All five response types conform to kinetic models based entirely on first-order rate expressions, which indicates that the heterogeneity among the response types arises from kinetic diversity within the DS terminal field. We report also that functionally distinct subregions of the DS express DA kinetic diversity in a selective manner. Thus, this study documents five response types, provides a thorough kinetic explanation for each of them, and confirms their differential association with functionally distinct subregions of this key DA terminal field. The dorsal striatum is composed of five significantly different dopamine domains (types 1-4 and slow, average ± SEM responses to medial forebrain bundle (MFB) stimulation are shown in the figure). Responses from each of these five domains exhibit significantly different ascending and descending kinetic profiles and return to a long lasting elevated dopamine state, termed the dopamine hang-up. All features of these responses are modeled with high correlation using first-order modeling as well as our recently published restricted diffusion model of evoked dopamine overflow. We also report that functionally distinct subregions of the dorsal striatum express selective dopamine kinetic diversity.

Dataset Information

Restricted diffusion of dopamine in the rat dorsal striatum.

Publications

Restricted diffusion of dopamine in the rat dorsal striatum.

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