Day/night differences in D1 but not D2 DA receptor protection from EEDQ denaturation in rats treated with continuous cocaine

Burger, Lynn Y.; Martin‐Iverson, Mathew T.

doi:10.1002/syn.890130104

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…Thus, this suggests that NPAS2 is not only involved in the initial vulnerability for cocaine-induced responses, but that chronic cocaine can also alter expression of NPAS2, leading to disrupted rhythms in dopamine receptor expression. Interestingly, continuous cocaine given via an osmotic pump for 14 days leads to an increase in D1 receptor occupation by dopamine during the day and a decrease in occupancy during the night compared to saline controls (47). The diurnal change in receptor function is abolished with co-administration of D1 antagonists, suggesting a feedback loop via D1 signaling.…”

Section: Discussionmentioning

confidence: 99%

Direct Regulation of Diurnal Drd3 Expression and Cocaine Reward by NPAS2

Ozburn

Falcón

Twaddle

et al. 2015

Biological Psychiatry

119

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Background Circadian gene disruptions are associated with the development of psychiatric disorders, including addiction. However, the mechanisms by which circadian genes regulate drug reward remain poorly understood. Methods We used mice with a mutation in Npas2, and AAV-shRNA mediated knock-down of Npas2 and Clock in the nucleus accumbens (NAc). We performed conditioned place preference (CPP) assays for cocaine. We utilized cell sorting techniques, qPCR and chromatin immunoprecipitation (ChIP) assays followed by deep sequencing (ChIP-seq). Results Npas2 mutants exhibit decreased sensitivity to cocaine reward which can be recapitulated with a knock-down of NPAS2 specifically in the NAc, demonstrating the functional importance of NPAS2 in this region. Interestingly, reducing CLOCK (a homologue of NPAS2) expression in the NAc had no effect, suggesting an important distinction in NPAS2 and CLOCK function. Furthermore, we find that NPAS2 expression is restricted to Drd1 expressing neurons, (i.e. “direct” pathway circuitry) while CLOCK is ubiquitous. Moreover, NPAS2 and CLOCK have distinct temporal patterns of DNA binding, and we identified novel and unique binding sites for each protein. We identified the Drd3 dopamine receptor as a direct transcriptional target of NPAS2 and find that NPAS2 knock-down in the NAc disrupts its diurnal rhythm in expression. Chronic cocaine treatment likewise disrupts the normal rhythm in Npas2 and Drd3 expression in the NAc, which may underlie behavioral plasticity in response to cocaine. Conclusions Together, these findings identify an important and novel role for the circadian protein, NPAS2, in the NAc in the regulation of dopamine receptor expression and drug reward.

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Section: Discussionmentioning

confidence: 99%

Direct Regulation of Diurnal Drd3 Expression and Cocaine Reward by NPAS2

Ozburn

Falcón

Twaddle

et al. 2015

Biological Psychiatry

119

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“…This apparent competition is consistent with a two-step mechanism of action for EEDQ, with the first step being a rapid and competitive binding to a recognition site, and the second step being a very slow reaction, and hence virtually irreversible, as has been described for the inactivation of an enzyme by EEDQ (Martin, Mancheño, & Arche, 1993). Protection from EEDQ-induced reduction in the density of dopamine receptors therefore provides an indication of in vivo occupation of both D 1 -like and D 2 -like receptor subtypes by endogenous and/or exogenous ligands (Burger & Martin-Iverson, 1993, 1994; Martin-Iverson & Burger, 1995). This method of receptor analysis was chosen to determine the effects of classical conditioning rats with cocaine and of a subsequent challenge cocaine injection on the relative densities of D 1 -like and D 2 -like receptors in the striatum and nucleus accumbens bound by dopamine, and of frontal cortical 5-HT 2 receptors bound by serotonin.…”

mentioning

confidence: 99%

Behavioral sensitization to cocaine, but not cocaine-conditioned behavior, is associated with increased dopamine occupation of its receptors in the nucleus accumbens.

Burechailo¹,

Martin‐Iverson²

1996

Behavioral Neuroscience

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Rats had repeated treatments with cocaine associated with a specific context (paired group). Evidence for classical conditioning of cocaine's motor-activity effects and context-specific behavioral sensitization to cocaine was obtained, relative to vehicle-treated (control) and pseudoconditioned (unpaired) groups. Only the paired group exhibiting context-specific behavioral sensitization had more dopamine bound to both D1-like and D2-like receptors in the nucleus accumbens than did rats in the control group receiving cocaine on the test day. No effects on receptor occupation were found in rats showing a classical conditioned response to a context previously paired with cocaine. Thus, sensitization to cocaine, but not classical conditioning of cocaine's behavioral effects, was associated with greater dopaminergic neurotransmission selectively in the nucleus accumbens.

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“…89,90 In the striatum, chronic cocaine administration leads to higher occupation of the DRD1 in the light phase and less during the dark phase which could explain the higher vulnerability to cocaine-induced reward during the light phase in rodents. 91 Acute cocaine administration induces changes in the NAc transcriptome mediated by DRD2-signaling. 92 Methamphetamine injections influence the circadian clock in different tissues, and it is suggested that the dopaminergic system participates in mediating these effects.…”

Section: Neurobiology Of Circadian Clock-reward Crosstalkmentioning

confidence: 99%

“…Interestingly, the reward effects induced by cocaine are mediated by increased DRD1 activation 89,90 . In the striatum, chronic cocaine administration leads to higher occupation of the DRD1 in the light phase and less during the dark phase which could explain the higher vulnerability to cocaine‐induced reward during the light phase in rodents 91 . Acute cocaine administration induces changes in the NAc transcriptome mediated by DRD2‐signaling 92 …”

Section: Neurobiology Of Circadian Clock‐reward Crosstalkmentioning

confidence: 99%

The circadian neurobiology of reward

et al. 2023

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Circadian clocks are important regulators of physiology and behavior. In the brain, circadian clocks have been described in many centers of the central reward system. They affect neurotransmitter signaling, neuroendocrine circuits, and the sensitivity to external stimulation. Circadian disruption affects reward signaling, promoting the development of behavioral and substance use disorders. In this review, we summarize our current knowledge of circadian clock‐reward crosstalk. We show how chronodisruption affects reward signaling in different animal models. We then translate these findings to circadian aspects of human reward (dys‐) function and its clinical implications. Finally, we devise approaches to and challenges in implementing the concepts of circadian medicine in the therapy of substance use disorders.

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Day/night differences in D1 but not D2 DA receptor protection from EEDQ denaturation in rats treated with continuous cocaine

Cited by 10 publications

References 46 publications

Direct Regulation of Diurnal Drd3 Expression and Cocaine Reward by NPAS2

Direct Regulation of Diurnal Drd3 Expression and Cocaine Reward by NPAS2

Behavioral sensitization to cocaine, but not cocaine-conditioned behavior, is associated with increased dopamine occupation of its receptors in the nucleus accumbens.

The circadian neurobiology of reward

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