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Gene Expression Is Altered in the Lateral Hypothalamus upon Activation of the mu Opioid Receptor
Author(s) -
Befort K.,
Filliol D.,
Darcq E.,
Ghate A.,
Matifas A.,
Lardenois A.,
Muller J.,
Thibault C.,
Dembele D.,
Poch O.,
Kieffer B.L.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1417.028
Subject(s) - μ opioid receptor , receptor , opioid , endocrinology , biology , medicine , opioid receptor , signal transduction , regulator of g protein signaling , glucocorticoid receptor , brain stimulation reward , microbiology and biotechnology , glucocorticoid , g protein , genetics , gtpase activating protein , nucleus accumbens
The lateral hypothalamus (LH) is a brain structure that controls hedonic properties of both natural rewards and drugs of abuse. Mu opioid receptors are known to mediate drug reward, but whether overstimulation of these receptors impacts on LH function has not been studied. Here we have used a genome‐wide microarray approach to identify LH responses to chronic mu opioid receptor activation at the transcriptional level. We have subjected wild‐type and mu opioid receptor knockout mice to an escalating morphine regimen, which produces severe physical dependence in wild‐type but not mutant animals. We have analyzed gene profiles in LH samples using the 430A.2 Affymetrix array and identified a set of 25 genes whose expression is altered by morphine in wild‐type mice only. The regulation was confirmed for a subset of these genes using real‐time quantitative PCR on samples from independent treatments. Altered expression of aquaporin 4, apolipoprotein D, and prostaglandin synthase is indicative of modified LH physiology. The regulation of two signaling genes (the serum glucocorticoid kinase and the regulator of G protein signaling 4) suggests that neurotransmission is altered in LH circuitry. Finally, the downregulation of apelin may indicate a potential role for this neuropeptide in opioid signaling and hedonic homeostasis. Altogether, our study shows that chronic mu opioid receptor stimulation induces gene expression plasticity in the LH and provides a unique collection of mu opioid receptor‐dependent genes that potentially contribute to alter reward processes in addictive diseases.