Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of dexamphetamine

Watanabe, Shizuhiko; Aono, Yuuta; Fusa, Koichi; Takada, Koji; Saigusa, Tadashi; Koshikawa, Noriaki; Cools, Alexander R.

doi:10.1016/j.neuroscience.2005.07.041

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…Specifically, AMPT inhibits tyrosine hydroxylase activity, thereby reducing newly synthesized DA [80], while reserpine depletes DA located in vesicular storage pools [81]. Because D-amphetamine primarily [82], but not exclusively [83,84], releases newly synthesized DA from cytosolic pools, its actions are more sensitive to AMPT than reserpine [61]. Consistent with this model, AMPT fully attenuated D-amphetamine-induced locomotor activity in the present study.…”

Section: Possible Neuronal Mechanisms Mediating Ketamine-and Psychostimulant-induced Locomotor Activitysupporting

confidence: 83%

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

McDougall

Rios

Apodaca

et al. 2020

Behavioural Brain Research

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The pattern of ketamine-induced locomotor activity varies substantially across ontogeny and according to sex. Although ketamine is classified as an NMDA channel blocker, it appears to stimulate the locomotor activity of both male and female rats via a monoaminergic mechanism. To more precisely determine the neural mechanisms underlying ketamine's actions, male and female preweanling and adolescent rats were pretreated with vehicle, the dopamine (DA) synthesis inhibitor ∝-methyl-DL-p-tyrosine (AMPT), or the serotonin (5-HT) synthesis inhibitor 4-chloro-DLphenylalanine methyl ester hydrochloride (PCPA). After completion of the pretreatment regimen, the locomotor activating effects of saline, ketamine, D-amphetamine, and cocaine were assessed during a 2 h test session. In addition, the ability of AMPT and PCPA to reduce dorsal striatal DA and 5-HT content was measured in male and female preweanling, adolescent, and adult rats. Results showed that AMPT and PCPA reduced, but did not fully attenuate, the ketamine-induced locomotor activity of preweanling rats and female adolescent rats. Ketamine (20 and 40 mg/kg) caused a minimal amount of locomotor activity in male adolescent rats, and this effect was not significantly modified by AMPT or PCPA pretreatment. When compared to ketamine, Damphetamine and cocaine produced different patterns of locomotor activity across ontogeny; moreover, AMPT and PCPA pretreatment affected psychostimulant-and ketamine-induced locomotion differently. When these results are considered together, it appears that both dopaminergic and serotonergic mechanisms mediate the ketamine-induced locomotor activity of preweanling and female adolescent rats. The dichotomous actions of ketamine relative to the psychostimulants in vehicle-, AMPT-, and PCPA-treated rats, suggests that ketamine modulates DA and 5-HT neurotransmission through an indirect mechanism.

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Section: Possible Neuronal Mechanisms Mediating Ketamine-and Psychostimulant-induced Locomotor Activitysupporting

confidence: 83%

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

McDougall

Rios

Apodaca

et al. 2020

Behavioural Brain Research

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“…1990; Hiroi and White 1990; DiLullo and Martin‐Iverson 1992; Heeringa and Abercrombie 1995; Sulzer et al . 1995; Sabol and Seiden 1998; Watanabe et al . 2005), our findings open the perspective that the individual‐specific susceptibility to cocaine (for references see introduction to article) and amphetamine (Piazza et al .…”

Section: Discussionmentioning

confidence: 99%

Differential contribution of storage pools to the extracellular amount of accumbal dopamine in high and low responders to novelty: effects of reserpine¹

Verheij

Cools

2006

Journal of Neurochemistry

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The present study examined the effects of reserpine on the extracellular concentration of accumbal dopamine in high responders (HR) and low responders (LR) to novelty rats. Reserpine reduced the baseline concentration of extracellular accumbal dopamine more in HR than in LR, indicating that the dopamine release is more dependent on reserpine-sensitive storage vesicles in non-challenged HR than in non-challenged LR. In addition, reserpine reduced the novelty-induced increase of the extracellular concentration of accumbal dopamine in LR, but not in HR, indicating that the dopamine release in response to novelty depends on reserpine-sensitive storage vesicles only in LR, not in HR. Our data clearly demonstrate that HR and LR differ in the characteristics of those monoaminergic storage vesicles that mediate accumbal dopamine release.

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“…A DA releaser can induce DA efflux from the cytoplasm via the DAT, but “free” DA molecules must be present in the cytoplasm in order for that process to occur. In vivo microdialysis studies in rats show that amphetamine increases extracellular DA concentrations by acting on non-vesicular and vesicular pools of cytoplasmic transmitter (Butcher et al, 1988; Florin et al, 1995; Watanabe et al, 2005). One hypothesis suggests that releasers deplete DA from vesicles because they are substrates of VMAT2, the primary transporter responsible for uptake of neurotransmitters into vesicles.…”

Section: Atypical Releasersmentioning

confidence: 99%

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

Reith

Blough

Hong

et al. 2015

Drug and Alcohol Dependence

119

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Background Treatment of Stimulant-Use Disorders remains a formidable challenge, and the dopamine transporter (DAT) remains a potential target for antagonist or agonist-like substitution therapies. Methods This review focuses on DAT ligands, such as benztropine, GBR 12909, modafinil, and DAT substrates derived from phenethylamine or cathinone that have atypical DAT-inhibitor effects, either in vitro or in vivo. The compounds are described from a molecular mechanistic, behavioral, and medicinal-chemical perspective. Results Possible mechanisms for atypicality at the molecular level can be deduced from the conformational cycle for substrate translocation. For each conformation, a crystal structure of a bacterial homolog is available, with a possible role of cholesterol, which is also present in the crystal of drosophila DAT. Although there is a direct relationship between behavioral potencies of most DAT inhibitors and their DAT affinities, a number of compounds bind to the DAT and inhibit dopamine uptake but do not share cocaine-like effects. Such atypical behavior, depending on the compound, may be related to slow DAT association, combined sigma-receptor actions, or bias for cytosol-facing DAT. Some structures are sterically small enough to serve as DAT substrates but large enough to also inhibit transport. Such compounds may display partial DA releasing effects, and may be combined with release or uptake inhibition at other monoamine transporters. Conclusions Mechanisms of atypical DAT inhibitors may serve as targets for the development of treatments for stimulant abuse. These mechanisms are novel and their further exploration may produce compounds with unique therapeutic potential as treatments for stimulant abuse.

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Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of dexamphetamine

Cited by 10 publications

References 24 publications

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

Differential contribution of storage pools to the extracellular amount of accumbal dopamine in high and low responders to novelty: effects of reserpine¹

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

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Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of dexamphetamine

Cited by 10 publications

References 24 publications

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

Differential contribution of storage pools to the extracellular amount of accumbal dopamine in high and low responders to novelty: effects of reserpine1

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

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Differential contribution of storage pools to the extracellular amount of accumbal dopamine in high and low responders to novelty: effects of reserpine¹