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Striatal dopamine and the temporal control of behavior.

ABSTRACT: Striatal dopamine strongly regulates how individuals use time to guide behavior. Dopamine acts on D1- and D2- dopamine receptors in the striatum. However, the relative role of these receptors in the temporal control of behavior is unclear. To assess this, we trained rats on a task in which they decided to start and stop a series of responses based on the passage of time and evaluated how blocking D1 or D2-dopamine receptors in the dorsomedial or dorsolateral striatum impacted performance. D2 blockade delayed the decision to start and stop responding in both regions, and this effect was larger in the dorsomedial striatum. By contrast, dorsomedial D1 blockade delayed stop times, without significantly delaying start times, whereas dorsolateral D1 blockade produced no detectable effects. These findings suggest that striatal dopamine may tune decision thresholds during timing tasks. Furthermore, our data indicate that the dorsomedial striatum plays a key role in temporal control, which may be useful for localizing neural circuits that mediate the temporal control of action.

SUBMITTER: De Corte BJ

PROVIDER: S-EPMC6516744 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Striatal dopamine and the temporal control of behavior.

De Corte Benjamin J BJ Wagner Lucia M LM Matell Matthew S MS Narayanan Nandakumar S NS

Behavioural brain research 20180910

Striatal dopamine strongly regulates how individuals use time to guide behavior. Dopamine acts on D1- and D2- dopamine receptors in the striatum. However, the relative role of these receptors in the temporal control of behavior is unclear. To assess this, we trained rats on a task in which they decided to start and stop a series of responses based on the passage of time and evaluated how blocking D1 or D2-dopamine receptors in the dorsomedial or dorsolateral striatum impacted performance. D2 blo ...[more]

PMID: 30213664

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Project description:Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn2+) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn2+ concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control subjects. Moreover, the level of striatal Zn2+ content in these subjects negatively correlated with plasma levels of benzoylecgonine, a cocaine metabolite indicative of recent use. In mice, repeated cocaine exposure increased synaptic Zn2+ concentrations in the caudate putamen (CPu) and nucleus accumbens (NAc). Cocaine-induced increases in Zn2+ were dependent on the Zn2+ transporter 3 (ZnT3), a neuronal Zn2+ transporter localized to synaptic vesicle membranes, as ZnT3 knockout (KO) mice were insensitive to cocaine-induced increases in striatal Zn2+. ZnT3 KO mice showed significantly lower electrically evoked DA release and greater DA clearance when exposed to cocaine compared to controls. ZnT3 KO mice also displayed significant reductions in cocaine locomotor sensitization, conditioned place preference (CPP), self-administration, and reinstatement compared to control mice and were insensitive to cocaine-induced increases in striatal DAT binding. Finally, dietary Zn2+ deficiency in mice resulted in decreased striatal Zn2+ content, cocaine locomotor sensitization, CPP, and striatal DAT binding. These results indicate that cocaine increases synaptic Zn2+ release and turnover/metabolism in the striatum, and that synaptically released Zn2+ potentiates the effects of cocaine on striatal DA neurotransmission and behavior and is required for cocaine-primed reinstatement. In sum, these findings reveal new insights into cocaine's pharmacological mechanism of action and suggest that Zn2+ may serve as an environmentally derived regulator of DA neurotransmission, cocaine pharmacodynamics, and vulnerability to cocaine use disorders.

Dataset Information

Striatal dopamine and the temporal control of behavior.

Publications

Striatal dopamine and the temporal control of behavior.

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