Journal article
A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine
PSYCHOPHARMACOLOGY, Vol.203(4), pp.703-711
05/01/2009
DOI: 10.1007/s00213-008-1417-z
PMCID: PMC2729782
PMID: 19050854
Abstract
We previously colocalized a quantitative trait locus (QTL) for sensitivity to the locomotor stimulant effects of methamphetamine (MA) with a QTL for expression of casein kinase 1 epsilon (Csnk1-E >) in the nucleus accumbens (NAc). Subsequently, we identified a single nucleotide polymorphism in CSNK1E (rs135745) that was associated with increased sensitivity to the subjective effects of d-amphetamine in healthy human subjects. Based on these results, we hypothesized that differential expression of Csnk1-E > causes differential sensitivity to MA-induced locomotor activity in mice.
In the present study, we used PF-670462 (PF), which is a selective inhibitor of Csnk1-E >, to directly evaluate the role of Csnk1-E > in the locomotor stimulant response to MA in male C57BL/6J mice.
We administered vehicle, PF, MA, or MA + PF, either via intraperitoneal injections or bilateral intra-NAc microinjections. We also examined Darpp-32 phosphorylation in mice receiving intraperitoneal injections.
Intraperitoneal PF (20-40 mg/kg) attenuated the locomotor stimulant response to MA (2 mg/kg) without affecting baseline activity. The high dose of PF also significantly inhibited MA-induced phosphorylation of Darpp-32, providing a potential mechanism by which Csnk1-E > contributes to MA-induced locomotor activity. Furthermore, microinjection of PF (5 mu g/side) into the NAc completely blocked the locomotor stimulant response to MA (2.5 mu g/side) without affecting baseline activity.
These results provide direct evidence that Csnk1-E > is crucial for the locomotor stimulant response to a moderate dose of MA and suggest that genetic polymorphisms affecting Csnk1-E > expression or function could influence sensitivity to amphetamines in both mice and humans.
Details
- Title: Subtitle
- A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine
- Creators
- Camron D Bryant - University of ChicagoMelissa E Graham - University of ChicagoMargaret G Distler - University of ChicagoMichaelanne B Munoz - University of ChicagoDongdong Li - University of ChicagoPaul Vezina - University of ChicagoGreta Sokoloff - University of ChicagoAbraham A Palmer - University of Chicago
- Resource Type
- Journal article
- Publication Details
- PSYCHOPHARMACOLOGY, Vol.203(4), pp.703-711
- DOI
- 10.1007/s00213-008-1417-z
- PMID
- 19050854
- PMCID
- PMC2729782
- NLM abbreviation
- Psychopharmacology (Berl)
- ISSN
- 0033-3158
- eISSN
- 1432-2072
- Publisher
- SPRINGER
- Number of pages
- 9
- Grant note
- Biological Sciences Collegiate Division Research endowments at the University of Chicago T32GM07281 / National Institute of General Medical Sciences Medical Scientist National Research Service Award
- Language
- English
- Date published
- 05/01/2009
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984256842302771
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