Time‐of‐day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens

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

doi:10.1002/syn.20552

Cited by 23 publications

(21 citation statements)

References 67 publications

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“…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%

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Ferris

España

Locke

et al. 2014

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

163

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: 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.

163

135

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“…Reproduction is considered highly dependent upon dopamine for its actions although the populations of DA neurons involved differ from those of the reward system (i.e., tuberoinfundibular and A15 vs. mesolimbic/mesocortical) (Goodman et al, 2010). Our laboratory and others have reported time-of-day differences in DAT and TH protein levels (Sleipness et al, 2007b, Webb et al, 2009a, Webb et al, 2009b) and in DAT function (Sleipness et al, 2008) in the mPFC and nucleus accumbens. Several other groups have also demonstrated diurnal or circadian changes in dopamine and its metabolites (O’Neill and Fillenz, 1985, Paulson and Robinson, 1994, Schade et al, 1995, Paulson and Robinson, 1996, Feenstra et al, 2000, Castaneda et al, 2004, Webb et al, 2009a) and in dopamine D2 receptor function (Tonissaar et al, 2006).…”

Section: Discussionmentioning

confidence: 68%

“…This would be expected to involve neurons in the VTA and NAc. Intriguingly, we have previously reported that rats initially held under 12L:12D and then housed in complete darkness displayed an unusual pattern of dopamine clearance in the mPFC (Sleipness et al, 2008). Cocaine, which inhibited mPFC dopamine clearance at all times of day in rats held under 12L:12D, showed no inhibition of clearance when rats were switched to complete darkness.…”

Section: Discussionmentioning

confidence: 86%

“…No handling or injections were administered prior to sacrifice. Tissue was collected and processed essentially as described previously (Sleipness et al, 2008) with some minor modifications as follows. For the mPFC, 50 μg of total protein was loaded; for the nucleus accumbens and dorsal striatum, 25 μg was loaded; and for the VTA, 16 μg was loaded onto 4-15% Tris-HCl gradient gels (Bio-Rad, Hercules, CA) and subjected to electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

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Photoperiodic suppression of drug reinstatement

et al. 2011

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The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our findings may have implications for novel targeting of circadian rhythms in the treatment of addiction.

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“…In summary, we are encouraged that following many years of research (Bruijnzeel & Gold, 2005; Dackis et al, 1984; Ebadi, Weiss, & Costa, 1970), the neurochemical mechanisms involved in the now established darkness-induced drinking paradigm has been further advanced (Sleipness, Jansen, Schenk, & Sorg, 2008). Based on the findings espoused in this hypothesis, the newer concepts of the role of both dopamine adducts (Hamilton, Blum, & Hirst, 1980; Sallstrom Baum, Hill, Kiianmaa, & Rommelspacher, 1999) and darkness-induced dopamine switching provides a fruitful avenue of investigation (El Halawani, Kang, Leclerc, Kosonsiriluk, & Chaiseha, 2009).…”

Section: Discussionmentioning

confidence: 99%

Hypothesizing Darkness Induced Alcohol Intake Linked to Dopaminergic Regulation of Brain Function

Blum¹,

Oscar‐Berman²,

Badgaiyan³

et al. 2014

PSYCH

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Understanding the role of neurotransmission in the prefrontal cortex and mesolimbic brain regions has become the subject of intensive neuroscience research worldwide. In the 1970s, our group provided evidence that rats exposed to darkness significantly augmented their alcohol intake. At that time, we proposed that melatonin was the culprit. At around the same time, our laboratory, amongst a few others, proposed that dopamine-adducts with acetaldehyde to induce alcohol intake both in rodents and in humans. While the work in these areas has declined considerably over the years, more recent scientifically sound studies continue to show the importance of these earlier controversial ideas involving alcohol abuse and alcoholism. A review of the literature has provided impetus to systematically access the newer genetic and molecular neurobiological findings relevant to the physiological and psychological motives for high alcohol consumption in animals and humans alike. Thus, we hypothesize that darkness-induced alcohol intake is linked not only to serotonergic-melatonin mechanisms, but also to dopaminergic regulation of brain mesolimbic pathways involving neuronal expression switching in response to long photoperiods affecting gene expression.

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Time‐of‐day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens

Cited by 23 publications

References 67 publications

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Photoperiodic suppression of drug reinstatement

Hypothesizing Darkness Induced Alcohol Intake Linked to Dopaminergic Regulation of Brain Function

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