GeneSet Information

Tier I GS86462 • Table 3: qPCR analysis of chronic morphine treatments for selected LH genes [DRG]

DESCRIPTION:

Chronic morphine - Morphine vs. Saline Real-time quantitative polymerase chain reaction Change in gene expression mu opioid Knockout (KO) mice Mice were injected twice daily with escalating doses of intraperitoneal morphine, beginning at 20 mg / kg and increasing to 100 mg / kg over 5 days. On day 6, only one injection of morphine was performed (100 mg / kg) and mice were then sacrificed for tissue collection 20 min after the last morphine injection. Control groups of mice were treated with saline under the same conditions. The 2-DeltaDeltaCt method was used to evaluate the differential expression level. A student t-test was performed to determine whether the fold change obtained for morphine-regulated genes is different from 1. Tested are gene expression levels using the same RNA samples as those used for the microarray hybridization experiment. Data were normalized using arbp reference gene. A second reference gene (beta-actin) was tested in each run as an internal control, and no change of expression was detected for either of these control genes. (NIF Table ID 430 [333])

LABEL:

Chronic morphine - Morphine vs. Saline

SCORE TYPE:

Correlation

DATE ADDED:

2010-11-03

DATE UPDATED:

2024-04-25

SPECIES:

URI:

http://neuinfo.org/

AUTHORS:

Befort K, Filliol D, Darcq E, Ghate A, Matifas A, Lardenois A, Muller J, Thibault C, Dembele D, Poch O, Kieffer BL

TITLE:

Gene expression is altered in the lateral hypothalamus upon activation of the mu opioid receptor.

JOURNAL:

Annals of the New York Academy of Sciences None 2008, Vol 1129, pp. 175-84

ABSTRACT:

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. PUBMED: 18591478
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Social Control, Formal (D012926)
Brain (D001921)
Gene Expression Regulation (D005786)
Students (D013334)
Homeostasis (D006706)
Animals (D000818)
RNA (D012313)
Street Drugs (D013287)
Reproducibility of Results (D015203)
Polymerase Chain Reaction (D016133)
Serum (D044967)
Mice (D051379)
Physiology (D010827)
Prostaglandin-Endoperoxide Synthases (D011451)
Mice, Knockout (D018345)
Therapeutics (D013812)
Role (D012380)
Neuropeptides (D009479)
Down-Regulation (D015536)
Receptors, Opioid, mu (D017450)
Pharmaceutical Preparations (D004364)
Tissues (D014024)
Hypothalamus (D007031)
Apolipoproteins D (D053399)
Mice, Inbred C57BL (D008810)
Aquaporin 4 (D051401)
Phosphotransferases (D010770)
Apolipoproteins (D001053)
GTP-Binding Proteins (D019204)
Reward (D012201)
Control Groups (D035061)
Morphine (D009020)
Set (Psychology) (D012718)
Injections (D007267)
Receptors, Opioid (D011957)
Synaptic Transmission (D009435)
Diagnosis-Related Groups (D003953)
serum (MA:0002502)
hypothalamus (MA:0000173)
brain (MA:0000168)
no abnormal phenotype detected (MP:0002169)
gene expression (GO:0010467)
signaling (GO:0023052)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351