Gene Expression Is Altered in the Lateral Hypothalamus upon Activation of the mu Opioid Receptor
| Autor: | Doulaye Dembélé, Emmanuel Darcq, Jean-Denis Muller, Aurélie Lardenois, Brigitte L. Kieffer, Olivier Poch, A. Ghate, Christelle Thibault, Dominique Filliol, Katia Befort, Audrey Matifas |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Lateral hypothalamus Hypothalamus Receptors Opioid mu Pharmacology Neurotransmission Biology Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Regulator of G protein signaling History and Philosophy of Science Internal medicine medicine Animals Receptor 030304 developmental biology Mice Knockout 0303 health sciences Morphine General Neuroscience Reproducibility of Results RGS17 Mice Inbred C57BL Endocrinology Gene Expression Regulation Opioid Knockout mouse μ-opioid receptor 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Annals of the New York Academy of Sciences. 1129:175-184 |
| ISSN: | 1749-6632 0077-8923 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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