Premium
Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, ΔFosB expression, and conditioned place preference to amphetamine and cocaine
Author(s) -
Marazziti Daniela,
Di Pietro Chiara,
Mandillo Silvia,
Golini Elisabetta,
Matteoni Rafaele,
TocchiniValentini Glauco P.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-175737
Subject(s) - conditioned place preference , amphetamine , phosphorylation , fosb , protein kinase b , chemistry , receptor , pharmacology , endocrinology , biology , biochemistry , dopamine , gene expression , gene
The orphan G‐protein‐coupled receptor 37 (GPR37) colocalizes with the dopamine (DA) transporter (DAT) in mouse nigrostriatal presynaptic membranes, and its genetic ablation in homozygous null‐mutant (GPR37‐KO) mice provokes the marked increase of plasma membrane expression of DAT, alteration of psychostimulant‐induced locomotor activity, and reduction of catalepsy induced by DA‐receptor antagonists. We report that extracts from GPR37‐KO mice displayed biochemical alterations of the nigrostriatal signaling pathways mediated by D1 and D2 dopaminergic receptors. Null‐mutant mice showed an increase of the basal phosphorylation level of the D2‐regulated Akt kinase. The basal phosphorylation of the D1‐activated ERK2 kinase was not altered, but acute treatments with amphetamine or cocaine failed to produce its specific increase, as detected in samples from wild‐type littermates. Furthermore, the chronic administration of cocaine to GPR37‐KO mice did not increase the expression of the ΔFosB transcription factor isoforms. Consistently, behavioral analysis showed that null‐mutant animals did not respond to the incentive properties of amphetamine or cocaine, in conditioned place preference tests. Thus, the lack of GPR37 affects both ERK2‐ and Akt‐mediated striatal signaling pathways, impairing the biochemical and behavioral responses typically induced by acute and chronic administration of psychostimulant drugs.—Marazziti, D., Di Pietro, C, Mandillo, S., Golini, E., Matteoni, R., and Tocchini‐Valentini, G. P. Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, ΔFosB expression, and conditioned place preference to amphetamine and cocaine. FASEB J. 25, 2071‐2081 (2011). www.fasebj.org