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Publication : Deletion of the GluR5 subunit of kainate receptors affects cocaine sensitivity and preference.

First Author  Gregus AM Year  2010
Journal  Neurosci Lett Volume  468
Issue  3 Pages  186-9
PubMed ID  19878705 Mgi Jnum  J:156898
Mgi Id  MGI:4421637 Doi  10.1016/j.neulet.2009.10.071
Citation  Gregus AM, et al. (2010) Deletion of the GluR5 subunit of kainate receptors affects cocaine sensitivity and preference. Neurosci Lett 468(3):186-9
abstractText  We have demonstrated previously that mice expressing a constitutive deletion of the kainate receptor subunit GluR5 (GluR5 KO) do not differ from wildtype (WT) littermates of a congenic C57BL/6 background with regard to both the development of morphine physical dependence as measured by naloxone-precipitated withdrawal signs and to morphine reward as revealed by the expression of conditioned place preference (CPP). However, unlike WT, GluR5 KO mice fail to develop antinociceptive tolerance following repeated systemic morphine administration. In this report, we examined the impact of GluR5 deletion on cocaine-mediated CPP and locomotor sensitization. Expression of CPP was evident in WT mice following repeated daily administration of 20mg/kg (but not 10mg/kg) i.p. cocaine. Interestingly, GluR5 KO mice exhibited enhanced cocaine preference as compared with WT mice at both 10 and 20mg/kg doses. In addition, while GluR5 KO mice did not differ from WT with respect to baseline locomotor activity, mutant mice demonstrated increased locomotor hyperactivity versus WT mice after repeated injection of 15mg/kg i.p. cocaine. Collectively, these data indicate that GluR5 appears to negatively modulate some psychostimulant and rewarding properties of cocaine, as demonstrated by heightened sensitization and salience in mutant mice.
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