DESCRIPTION:

Chronic morphine - Morphine vs. Placebo DNA microarray Change in mRNA expression Animals underwent surgery for subcutaneous implantation of either a control (Placebo to Morphine Base Implant Pellet) or morphine pellet (25 mg Morphine Base Implant Pellet) on the dorsal aspect of the neck. The composition of the pellets was identical (microcrystalline cellulose, 149 mg; magnesium stearate, 1.5 mg; colloidal silicon dioxide, 2.5 mg) except for the addition of 25 mg of purified morphine. While the animal was under anesthesia, a 1/4-inch slit was made in the skin, the pellet inse Used dChip algorithm (version 1.3). Invariant Set Normalization and PM-MM modeling; The nominal p value was determined using dChip (which down-weights unreliable expression data), testing whether the mean difference between two groups equals to zero by the unpaired t-test. mRNAs showing a P < 0.05 and greater than >= 1.7 fold change. Median False-Discovery Rate (FDR) estimates were significantly higher (roughly 20%) for contrasts within strains. (NIF Method ID 336)

LABEL:

Chronic morphine - Morphine vs. Placebo

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.0449

GENES IN THRESHOLD:

0

DATE ADDED:

2010-11-03

DATE UPDATED:

2024-04-25

SPECIES:

URI:

http://neuinfo.org/

AUTHORS:

Grice DE, Reenil I, Mnnist PT, Brooks AI, Smith GG, Golden GT, Buxbaum JD, Berrettini WH

TITLE:

Transcriptional profiling of C57 and DBA strains of mice in the absence and presence of morphine.

JOURNAL:

BMC genomics Mar 2007, Vol 8, pp. 76

ABSTRACT:

BACKGROUND: The mouse C57BL/6 (C57) and DBA/2J (DBA) inbred strains differ substantially in many aspects of their response to drugs of abuse. The development of microarray analyses represents a genome-wide method for measuring differences across strains, focusing on expression differences. In the current study, we carried out microarray analysis in C57 and DBA mice in the nucleus accumbens of drug-naïve and morphine-treated animals. RESULTS: We identified mRNAs with altered expression between the two strains. We validated the mRNA expression changes of several such mRNAs, including Gnb1, which has been observed to be regulated by several drugs of abuse. In addition, we validated alterations in the enzyme activity of one mRNA product, catechol-O-methyltransferase (Comt). Data mining of expression and behavioral data indicates that both Gnb1 and Comt expression correlate with aspects of drug response in C57/DBA recombinant inbred strains. Pathway analysis was carried out to identify pathways showing significant alterations as a result of treatment and/or due to strain differences. These analyses identified axon guidance genes, particularly the semaphorins, as showing altered expression in the presence of morphine, and plasticity genes as showing altered expression across strains. Pathway analysis of genes showing strain by treatment interaction suggest that the phosphatidylinositol signaling pathway may represent an important difference between the strains as related to morphine exposure. CONCLUSION: mRNAs with differing expression between the two strains could potentially contribute to strain-specific responses to drugs of abuse. One such mRNA is Comt and we hypothesize that altered expression of Comt may represent a potential mechanism for regulating the effect of, and response to, multiple substances of abuse. Similarly, a role for Gnb1 in responses to multiple drugs of abuse is supported by expression data from our study and from other studies. Finally, the data support a role for semaphorin signaling in morphine effects, and indicate that altered expression of genes involved in phosphatidylinositol signaling and plasticity might also affect the altered drug responses in the two strains. PUBMED: 17367521
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