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. 2007 Feb;52(2):430-5.
doi: 10.1016/j.neuropharm.2006.08.012. Epub 2006 Oct 2.

Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus

Cynthia Marie-Claire  1 , Cindie Courtin, Amelie Robert, Xavier Gidrol, Bernard P Roques, Florence Noble
Affiliations

Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus

Cynthia Marie-Claire et al. Neuropharmacology. 2007 Feb.

Abstract

Opiates addiction is characterized by its long-term persistence. In order to study the enduring changes in long-term memory in hippocampus, a pivotal region for this process, we used suppression subtractive hybridization to compare hippocampal gene expression in morphine and saline-treated rats. Animals were subjected to an extended place preference paradigm consisting of four conditioning phases. Sensitization to the reinforcing effects of the drug occurred after three conditioning phases. After 25 days of treatment rats were euthanized and the complementary DNA (cDNA) from the hippocampus of morphine-dependent and saline-treated animals were then screened for differentially expressed cDNAs. The selected 177 clones were then subjected to a microarray procedure and 20 clones were found differentially regulated. The pattern of regulated genes suggests impairments in neurotransmitter release and the activation of neuroprotective pathways.

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Figures

Figure 1
Figure 1
A) Summary of the experimental protocol used in the conditioned place preference procedure B) conditioned place preference induced by morphine (5 mg/kg, s.c.) for test sessions T1 to T4. Data are expressed as scores (means + SEM) calculated as the difference between postconditioning and preconditioning time spent in the compartment associated with the drug. * p<0.05, *** p<0.001 versus the saline group; ## p<0.01 versus test session T2 (Newman Keuls test).
Figure 2
Figure 2
Representative differential screening of clones from the up- and down-regulated libraries. Nylon membranes were spotted with colonies from the down-regulated (A) or the up-regulated (B) libraries and hybridized with labeled probe from subtractive up-regulated cDNAs. Arrows (→) indicate positive colonies in the up-regulated library which predominantly hybridized with the up-regulated cDNAs probe.
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