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-epsilon) 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-epsilon 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-epsilon, to directly evaluate the role of Csnk1-epsilon 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-epsilon contributes to MA-induced locomotor activity. Furthermore, microinjection of PF (5 microg/side) into the NAc completely blocked the locomotor stimulant response to MA (2.5 microg/side) without affecting baseline activity.
These results provide direct evidence that Csnk1-epsilon is crucial for the locomotor stimulant response to a moderate dose of MA and suggest that genetic polymorphisms affecting Csnk1-epsilon expression or function could influence sensitivity to amphetamines in both mice and humans.
Pharmacology, Toxicology and Pharmaceutical Science
1
4%
Other
1
4%
Unknown
6
24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 January 2017.
All research outputs
#7,380,173
of 33,931,414 outputs
Outputs from Psychopharmacology
#1,851
of 7,181 outputs
Outputs of similar age
#41,012
of 242,837 outputs
Outputs of similar age from Psychopharmacology
#17
of 41 outputs
Altmetric has tracked 33,931,414 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 7,181 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.8. This one has gotten more attention than average, scoring higher than 66% of its peers.
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We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
