Background Chronic opiate use produces molecular and cellular adaptations in the

Background Chronic opiate use produces molecular and cellular adaptations in the nervous system that lead to tolerance, physical dependence, and addiction. Tsc22d3 and Nfkbia) was identified as being mediated via the glucocorticoid receptor (GR). Further studies revealed that blockade of the GR altered morphine-induced locomotor activity and development of physical dependence. Conclusion Our results indicate that there are differences between strains in the magnitude of transcriptional response to acute morphine treatment and in the degree of tolerance in gene expression observed 4199-10-4 manufacture after chronic morphine treatment. Using whole-genome transcriptional SH3RF1 analysis of morphine effects in the striatum, we were able to reveal multiple physiological factors that may influence opioid-related phenotypes and to relate particular gene networks to this complex trait. The results also suggest the possible involvement of GR-regulated genes in mediating behavioral response to morphine. Background Opioids are considered to be among the most potent drugs for relieving severe chronic pain. Long-term morphine treatment is undesirable because of the development of tolerance to its analgesic effects and physical dependence. On the other hand, prolonged abuse 4199-10-4 manufacture of opiates leads to drug addiction – a chronic, relapsing disorder with a complex mechanism. Accumulating evidence is converging to suggest that formation 4199-10-4 manufacture of opioid addiction involves changes in synaptic structure and neuronal plasticity [1]. These long-lasting neuroadaptations probably include compound changes in gene expression in the mesocorticolimbic system of the brain [2]. The major substrates of the molecular and cellular mechanisms of opioid addiction are suggested to be the dorsal and ventral striatum. Morphine administration enhances the release of dopamine in both the dorsal striatum and nucleus accumbens [3]. It is well established that the nucleus accumbens, a ventral subregion that receives dopaminergic projections from the ventral tegmental area, is related to the reward properties of opioids [4]. The dorsal part of the striatum is a brain region that is implicated in habit learning, which is a fundamental component of addiction [5]. It is well known that drugs of abuse stimulate the transcription of numerous genes in several brain regions [6,7]. Moreover, a significant contribution of genetic factors to vulnerability to the addictive action of opiates and other addictive drugs is well established [8]. Several other effects of opioid action, for example analgesia and hypothermia, are also likely to be determined by combinations of genetic factors [9]. In contrast, the influence of genotype on genomic response to opioids and the association between changes in gene expression and development of the rewarding and addictive effects are poorly characterized. Inbred strains of mice with well described phenotypes provide valuable models in which to analyze interactions between genetic background, and behavioral and transcriptional responses to the drug. To separate the relationship between the different effects of morphine and the gene expression profiles in the striatum, we compared responses to acute and chronic drug treatment across four mouse strains with extreme opioid-related phenotypes (C57BL/6J, DBA/2J, 129P3/J, and SWR/J). Two commonly used inbred strains of mice, C57BL/6J and DBA/2J, exhibit remarkable differences in morphine-induced locomotor activation and conditional place preference [10,11]. Compared with the other strains, C57BL/6J mice were found to have the greatest preference for oral self-administered morphine [12]. Furthermore, the 129P3/J strain failed to develop physical dependence and tolerance, whereas extraordinary sensitivity to opioid withdrawal was observed in SWR/J mice [13]. Our prior comparison of gene expression profiles of na?ve animals from the selected inbred mouse strains indicated diversity at the level of several hundreds of transcripts in the striatum [14]. Here, we use microarray technology to obtain a profile of genes that are regulated by acute and chronic morphine in the striatum of the four mouse strains. Our ultimate goal is to link particular genes, regulatory elements, and specific signaling pathways with opioid-related traits. To this end, we have combined gene expression profiling with bioinformatic approaches and behavioral testing. The results presented here identify several novel morphine-responsive genes that may modulate the molecular as well as behavioral response to morphine and may.