Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Bryant, Camron D.; Parker, Clarissa C.; Zhou, Lili; Olker, Christopher; Chandrasekaran, Ramalakshmi Y.; Wager, Travis T.; Bolivar, Valerie J.; Loudon, A. S. I.; Vitaterna, Martha Hotz; Turek, Fred W.; Palmer, Abraham A.

doi:10.1038/npp.2011.287

Cited by 57 publications

(74 citation statements)

References 58 publications

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“…A further limitation of existing pharmacological studies is that the contribution of specific CK-1 isoforms to these drug-induced behaviors is unknown. Current evidence suggests that CSNK1D could normally serve to facilitate drug-induced behaviors whereas CSNK1E could normally serve to inhibit them (Bryant et al ., 2009a, Bryant et al ., 2012, Zhou et al ., 2010). Pharmacological inhibition with a CSNK1E-preferring compound increased psychostimulant and opioid activity and genetic knockout of Csnk1e increased psychostimulant-induced locomotor activity (Bryant et al ., 2009a, Bryant et al ., 2012), which is consistent with a negative regulatory role for the epsilon isoform in acute drug sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

Goldberg

Kirkpatrick

Yazdani

et al. 2017

Genes Brain and Behavior

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Genetic and pharmacological studies indicate that casein kinase-1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0.2 mg/kg i.p.) as well as enhanced sensitivity to low-dose fentanyl reward (0.05 mg/kg). Interestingly, female knockout mice also showed a markedly greater escalation in consumption of sweetened palatable food – a behavioral pattern consistent with binge eating that also depends on mu opioid receptor activation. No difference was observed in fentanyl analgesia in the 52.5°C hot plate assay (0–0.4 mg/kg), naloxone conditioned place aversion (4 mg/kg), or methamphetamine conditioned place preference (0–4 mg/kg). To identify molecular adaptations associated with increased drug and food behaviors in knockout mice, we completed transcriptome analysis via mRNA sequencing of the striatum. Enrichment analysis identified terms associated with myelination and axon guidance and pathway analysis identified a differentially expressed gene set predicted to be regulated by the Wnt signaling transcription factor, Tcf7l2. To summarize, Csnk1e deletion increased mu opioid receptor-dependent behaviors, supporting previous studies indicating an endogenous negative regulatory role of Csnk1e in opioid behavior.

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Section: Introductionmentioning

confidence: 99%

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

Goldberg

Kirkpatrick

Yazdani

et al. 2017

Genes Brain and Behavior

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“…Several mouse genetic resources have been employed for the study of addiction including the BXD recombinant inbred strains (Belknap and Crabbe 1992; Belknap et al 1993; Crabbe et al 1994; Gallaher et al 1996; Grisel et al 1997; Kest et al 2004; Philip et al 2010; Phillips et al 1998; Roberts et al 1995; Tarantino et al 1998), F 2 hybrid crosses (Bergeson et al 2001; Doyle et al 2008; Ferraro et al 2005; Kest et al 2004), the Hybrid Mouse Diversity Panel (Bryant et al 2012a; Ghazalpour et al 2012; Park et al 2011; Parker et al 2012a), and advanced intercross lines (Bryant et al 2012b; Parker et al 2012a; Parker et al 2012b; Samocha et al 2010). While these resources have enabled substantial progress in the understanding of mechanisms underlying the effects of addictive drugs, each has some limitations in power, precision, genetic diversity, and genetic architecture.…”

Section: Discussionmentioning

confidence: 99%

Association of novelty-related behaviors and intravenous cocaine self-administration in Diversity Outbred mice

et al. 2014

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Rationale Preference for and reaction to novelty are strongly associated with addiction to cocaine and other drugs. However, the genetic variants and molecular mechanisms underlying these phenomena remain largely unknown. Although the relationship between novelty- and addiction-related traits has been observed in rats, studies in mice have failed to demonstrate this association. New, genetically diverse, high-precision mouse populations including Diversity Outbred (DO) mice provide an opportunity to assess an expanded range of behavioral variation enabling detection of associations of novelty- and addiction-related traits in mice. Methods To examine the relationship between novelty- and addiction-related traits, male and female DO mice were tested on open field exploration, hole board exploration, and novelty preference followed by intravenous cocaine self-administration (IVSA; ten 2-hour sessions of fixed-ratio 1 and one 6-hour session of progressive ratio). Results We observed high variation of cocaine IVSA in DO mice with 43% reaching and 57% not reaching conventional acquisition criteria. As a group, mice that did not reach these criteria still demonstrated significant lever discrimination. Mice experiencing catheter occlusion or other technical issues (n = 17) were excluded from analysis. Novelty-related behaviors were positively associated with cocaine IVSA. Multivariate analysis of associations among novelty- and addiction-related traits revealed a large degree of shared variance (45%). Conclusions Covariation among cocaine IVSA and novelty-related phenotypes in DO mice indicates that this relationship is amenable to genetic dissection. The high genetic precision and phenotypic diversity in the DO may facilitate discovery of previously undetectable mechanisms underlying predisposition to develop addiction disorders.

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“…Mice were 2-3 months of age on the first day of behavioral testing (F 2 range was 53-71 days; AIL range was 50-76 days). All mice went through an identical testing sequence: first, we measured open field (OF) behavior as part of a locomotor testing paradigm (Bryant et al 2012); 1 week later, we began the conditioned fear (CF) paradigm. All experiments were performed in accordance with the National Institutes of Health guidelines for care and use of laboratory animals.…”

Section: Behavioral Testingmentioning

confidence: 99%

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

et al. 2014

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Genetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F 2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F 2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F 2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of "realized relatedness." QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F 2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL.

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Csnk1e Is a Genetic Regulator of Sensitivity to Psychostimulants and Opioids

Cited by 57 publications

References 58 publications

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

Casein kinase 1‐epsilon deletion increases mu opioid receptor‐dependent behaviors and binge eating1

Association of novelty-related behaviors and intravenous cocaine self-administration in Diversity Outbred mice

High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

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