Diurnal differences in dopamine transporter and tyrosine hydroxylase levels in rat brain: Dependence on the suprachiasmatic nucleus

Sleipness, Evan P.; Sorg, Barbara A.; Jansen, Heiko T.

doi:10.1016/j.brainres.2006.10.063

Cited by 128 publications

(115 citation statements)

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“…Therefore, we examined both the levels and activity of TH across the four time points in the light/dark cycle in both WT and DAT KO mice. Similar to previously published reports (38,39), Western blot analysis revealed that TH levels oscillated in a manner similar to [DA] ext in WT mice. Indeed, Fig.…”

Section: Oscillations In the Level And Activity Of Th Cannot Account supporting

confidence: 73%

“…Diurnal variation in the density of cellsurface DAT (38,39) and some changes in DA uptake kinetics have been noted (41,42); however, no work has systematically compared variations in DA uptake to the number of parameters investigated herein. Therefore, our initial experiments focused on examining the extent to which uptake fluctuated across the light/dark cycle.…”

Section: Discussionmentioning

confidence: 99%

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Dopamine transporters govern diurnal variation in extracellular dopamine tone

Ferris

España

Locke

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

161

135

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The majority of neurotransmitter systems shows variations in state-dependent cell firing rates that are mechanistically linked to variations in extracellular levels, or tone, of their respective neurotransmitter. Diurnal variation in dopamine tone has also been demonstrated within the striatum, but this neurotransmitter is unique, in that variation in dopamine tone is likely not related to dopamine cell firing; this is largely because of the observation that midbrain dopamine neurons do not display diurnal fluctuations in firing rates. Therefore, we conducted a systematic investigation of possible mechanisms for the variation in extracellular dopamine tone. Using microdialysis and fast-scan cyclic voltammetry in rats, as well as wild-type and dopamine transporter (DAT) knock-out mice, we demonstrate that dopamine uptake through the DAT and the magnitude of subsecond dopamine release is inversely related to the magnitude of extracellular dopamine tone. We investigated dopamine metabolism, uptake, release, D2 autoreceptor sensitivity, and tyrosine hydroxylase expression and activity as mechanisms for this variation. Using this approach, we have pinpointed the DAT as a critical governor of diurnal variation in extracellular dopamine tone and, as a consequence, influencing the magnitude of electrically stimulated dopamine release. Understanding diurnal variation in dopamine tone is critical for understanding and treating the multitude of psychiatric disorders that originate from perturbations of the dopamine system. circadian | caudate-putamen | nucleus accumbens T he dopamine transporter (DAT) is a transmembrane protein that removes dopamine (DA) from the extracellular space to terminate signaling at pre-and postsynaptic receptors. Extensive evidence indicates that aberrant DAT function may be involved in many neuropsychiatric illnesses, including attention deficit hyperactivity disorder (1, 2), depression (3, 4), substance abuse disorders (5, 6), schizophrenia (7-9), and anxiety disorders (10, 11). Our current understanding of the role of the DAT under physiologically normal conditions is that of a homeostatic regulator. This basic hypothesis was confirmed in work using DAT knock-out (KO) mice, where extracellular DA levels ([DA] ext ) and corresponding locomotor activity are substantially higher than in WT animals (12, 13). In addition, up-or down-regulation of the DAT is regarded as a compensatory plasticity to "normalize" [DA] ext in the context of repeated exposure to abused drugs (5,14,15).Despite this progress in understanding DAT function, much less work has been dedicated to understanding the role of the DAT and other presynaptic modulators of [DA] Despite the limited mechanistic understanding of the complex relationship between [DA] ext and nerve terminal function, behaviors known to be governed by DA are strongly influenced by diurnal cycles. For example, behaviors that measure reinforcement and reward, such as psychostimulant self-administration and conditioned place preference, fluctuate markedly a...

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Section: Oscillations In the Level And Activity Of Th Cannot Account supporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Ferris

España

Locke

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

161

135

View full text Add to dashboard Cite

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“…Furthermore, identification of specific clock binding elements (E-boxes) within the promoter regions of the dopamine transporter, dopamine D1A receptor, and tyrosine hydroxylase genes (Kawarai et al, 1997;Weber et al, 2004) supports the existence of an interaction between circadian clocks and dopaminergic neurotransmission. Indeed, it was discovered that the SCN is at least partially responsible for the presence of normal day/night differences in dopamine transporter and tyrosine hydroxylase protein expression in the nucleus accumbens, mPFC, and caudate (Sleipness et al, 2007b). A contribution of the SCN in the day/night variation in cocaine-seeking behavior in rats has also been reported (Sleipness et al, 2007a).…”

Section: Discussionmentioning

confidence: 99%

Circadian modulation of interval timing in mice

et al. 2011

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Temporal perception is fundamental to environmental adaptation in humans and other animals. To deal with timing and time perception, organisms have developed multiple systems that are active over a broad range of order of magnitude, the most important being circadian timing, interval timing and millisecond timing. The circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, and is driven by a selfsustaining oscillator with a period close to 24 h. Time estimation in the second-to-minutes range -known as interval timing -involves the interaction of the basal ganglia and the prefrontal cortex. In this work we tested the hypothesis that interval timing in mice is sensitive to circadian modulations. Animals were trained following the peak-interval (PI) procedure. Results show significant differences in the estimation of 24-second intervals at different times of day, with a higher accuracy in the group trained at night, which were maintained under constant dark (DD) conditions. Interval timing was also studied in animals under constant light (LL) conditions, which abolish circadian rhythmicity. Mice under LL conditions were unable to acquire temporal control in the peak interval procedure.Moreover, short time estimation in animals subjected to circadian desynchronizations (modeling jet lag-like situations) was also affected. Taken together, our results indicate that short-time estimation is modulated by the circadian clock.© 2010 Elsevier B.V. All rights reserved. Keywords:Circadian rhythms Interval timingBasal ganglia Suprachiasmatic nuclei IntroductionTiming and time perception are fundamental to survival and goal reaching in humans and other animals. Organisms have developed diverse mechanisms for timing across different scales, the most important being circadian timing, interval timing and millisecond timing . The circadian pacemaker -which is driven by a self-sustaining oscillator with a period close to 24 h -is located in the suprachiasmatic nuclei (SCN) of the hypothalamus (Dunlap et al., 2004), and the principal signal that adjusts its activity is the light-dark cycle (Morin and Allen, 2006;Golombek and Rosenstein, 2010). The molecular mechanism of the endogenous circadian clock is comprised by interlocked transcription-translation feedback loops (Reppert and Weaver, 2002). On the other hand, the perception of shorter durations in the seconds-to-minutes range, known as interval timing, is crucial to learning, memory, decision making and other cognitive

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“…A potential indirect pathway from the SCN to the ventral tegmental area (VTA) and dorsal raphe nucleus via the dorsomedial hypothalamic nucleus has also been described (Deurveilher and Semba 2005). There is also a dependence on the SCN for the circadian regulation of certain genes in the dopaminergic neurons of the VTA (Sleipness et al 2007). The SCN could also influence rhythms in other brain regions through its control of circulating hormones and peptides.…”

Section: Regulation Of These Rhythms By the Scnmentioning

confidence: 99%

“…In addition, our recent studies suggest that Clock functions in the dopamine cells of the VTA to regulate the expression of other circadian genes and several genes involved in dopaminergic transmission including the rate-limiting enzyme in dopamine synthesis tyrosine hydroxylase (TH) (McClung et al 2005;Roybal et al 2007). Interestingly, TH and a number of other genes involved in dopaminergic transmission such as cholecystokinin, the dopamine transporter, and various dopamine receptors, all have a robust circadian rhythm in expression, suggesting that they might be regulated by circadian genes (Weber et al 2004;Sleipness et al 2007). We have found that the Clock mutant mice have an increase in dopaminergic activity in the VTA that correlates with their manic-like behavior (Fig.…”

Section: The Circadian Genes In Other Brain Regionsmentioning

confidence: 99%

Role for theClockGene in Bipolar Disorder

McClung¹

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Nearly all patients with bipolar disorder have severely disrupted circadian rhythms. Treatment with mood stabilizers can restore these daily rhythms, and this is correlated with patient recovery. However, it is still uncertain whether clock abnormalities are the cause of bipolar disorder or if these rhythm disruptions are secondary to alterations in other circuits. Furthermore, the mechanism by which the circadian clock might influence mood is still unclear. With cloning and characterization of the circadian genes and recent advances in molecular biology, we are starting to understand this strong association between circadian rhythms and bipolar disorder. Recent human genetic and mouse behavioral studies indicate that the Clock gene is particularly relevant in the mood disruptions associated with this disorder. Furthermore, it appears that Clock expression outside of the central pacemaker of the suprachiasmatic nucleus (SCN) is involved in mood regulation. In this chapter, the evidence linking circadian rhythms, the Clock gene, and bipolar disorder is discussed, along with the possible biology that underlies this connection.

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Diurnal differences in dopamine transporter and tyrosine hydroxylase levels in rat brain: Dependence on the suprachiasmatic nucleus

Cited by 128 publications

References 50 publications

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Circadian modulation of interval timing in mice

Role for theClockGene in Bipolar Disorder

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