Abstract EN:

The opioid system consists of three G-protein coupled receptors, mu, delta, and kappa, which are stimulated by a family of endogenous opioid peptides like beta-endorphin and exogenous ligands such as morphine. It is believed that the repeated opiate administration alters gene expression in different brain regions of rodents, an effect which may contribute to plastic changes associated with addictive behaviour. Oligonucleotide and cDNA microarrays are the two most commonly used methods to profile the expression of thousands of genes in parallel. Gene expression studies performed by microarray analysis or by parallel measurements of the mRNA of multiple candidate genes have become a powerful tool to screen gene expression in the brain after application of drugs of abuse. Studies have shown that the reinforcing properties of morphine, alcohol, cannabinoids and nicotine are abolished or diminished in mice lacking the mu-opioid receptor. The genetic approach therefore highlights mu opioid receptors as convergent molecular switches which mediate reinforcement following direct (eg: morphine) or indirect activation (non-opioid drugs). Use of the mu-opioid receptor knockout mice would therefore help in identifying the genes, downstream of the mu-opioid receptor, that are commonly dysregulated following long term exposure to drugs of abuse. My thesis work involved establishment and use of cDNA and oligonucleotide microarrays screening tools in our laboratory to identify the transcriptional adaptations that occur on activation or in absence of the opioid receptors. I have also characterised obese phenotype observed in the triple opioid receptor knockout mice. Our laboratory is also interested in performing region-specific deletions of the opioid system and is therefore in the process of developing transgenic mice under region-specific promoters. A part of my thesis work also involved searching for region-specific markers for brain areas relevant in drug addiction.