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Hippocampal CA1 region shows differential regulation of gene expression in mice displaying extremes in behavioral sensitization to amphetamine: relevance for psychosis susceptibility?

Authors :
Datson NA
Speksnijder N
de Jong IE
Steenbergen PJ
Vielsted Christensen K
Potempa K
Torleif Pedersen J
Egebjerg J
Kallunki P
Nielsen EB
de Kloet ER
Didriksen M
Source :
Psychopharmacology [Psychopharmacology (Berl)] 2011 Oct; Vol. 217 (4), pp. 525-38. Date of Electronic Publication: 2011 May 03.
Publication Year :
2011

Abstract

Rationale: Psychosis susceptibility is mediated in part by the dopaminergic neurotransmitter system. In humans, individual differences in vulnerability for psychosis are reflected in differential sensitivity for psychostimulants such as amphetamine. We hypothesize that the same genes and pathways underlying behavioral sensitization in mice are also involved in the vulnerability to psychosis.<br />Objectives: The aim of the current study was to investigate which genes and pathways may contribute to behavioral sensitization in different dopaminergic output areas in the mouse brain.<br />Methods: We took advantage of the naturally occurring difference in psychostimulant sensitivity in DBA/2 mice and selected animals displaying extremes in behavioral sensitization to amphetamine. Subsequently, the dopamine output areas, prefrontal cortex, nucleus accumbens, and cornu ammonis 1 (CA1) area of the hippocampus, were isolated by laser microdissection and subjected to DNA microarray analysis 1 h after a challenge dose of amphetamine.<br />Results: A large number of genes with differential expression between high and low responders were identified, with no overlap between brain regions. Validation of these gene expression changes with real-time quantitative polymerase chain reaction demonstrated that the most robust and reproducible effects on gene expression were in the CA1 region of the hippocampus. Interestingly, many of the validated genes in CA1 are members of the cAMP response element (CRE) family and targets of the glucocorticoid receptor (GR) and myocyte enhancer factor 2 (Mef2) transcription factors.<br />Conclusion: We hypothesize that CRE, Mef2, and GR signaling form a transcription regulating network, which underlies differential amphetamine sensitivity, and therefore, may play an important role in susceptibility to psychosis.

Details

Language :
English
ISSN :
1432-2072
Volume :
217
Issue :
4
Database :
MEDLINE
Journal :
Psychopharmacology
Publication Type :
Academic Journal
Accession number :
21537941
Full Text :
https://doi.org/10.1007/s00213-011-2313-5