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Prescription opioid abuse, for example of oxycodone, is a pressing public health issue. This study focuses on how chronic oxycodone self-administration (SA) affects the reward pathways in the mouse brain. In this study, we tested the hypothesis that the expression of reward-related genes in the ventral and dorsal striatum, areas involved in different aspects of opioid addiction models, was altered within 1 h after chronic oxycodone SA, using transcriptome-wide sequencing (RNA-seq). Based on results from earlier human genetic and rodent preclinical studies, we focused on a set of genes that may be associated with the development of addictive diseases and the rewarding effect of drugs of abuse, primarily in the opioid, stress response and classical neurotransmitter systems. We found that 32 transcripts in the ventral striatum, and 7 in the dorsal striatum, were altered significantly in adult mice that had self-administered oxycodone (n = 5) for 14 consecutive days (4 h/day) compared with yoked saline controls (n = 5). The following 5 genes in the ventral striatum showed experiment-wise significant changes: proopiomelanocortin (Pomc) and serotonin 5-HT-2A receptor (Htr2a) were upregulated; serotonin receptor 7 (Htr7), galanin receptor1 (Galr1) and glycine receptor 1 (Glra1) were downregulated. Some genes detected by RNA-seq were confirmed by quantitative polymerase chain reaction (qPCR). Conclusion: A RNA-seq study shows that chronic oxycodone SA alters the expression of several reward-related genes in the dorsal and ventral striatum. These results suggest potential mechanisms underlying neuronal adaptation to chronic oxycodone self-exposure, of relevance to our mechanistic understanding of prescription opioid abuse.

Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction.Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European).A total of 11 SNPs in eight genes showed nominally significant associations (P0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3 rs7165224; DBI rs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2A rs1650420 were previously reported in associations with drug addiction or related phenotypes.The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction.

Aims: Retention in methadone maintenance treatment (MMT) for at least one year has been associated with positive outcomes. Predictors of retention in MMT have traditionally collapsed across gender. This study hypothesizes that predictors of retention will differ between men and women, and aims to determine which factors best predict retention for each gender. Methods: Data were collected from the files of 290 patients (173 M, 117 F) admitted to MMT at an outpatient clinic in Detroit between 2002 and 2007. The modal participant was a 50-year old African American (84.8%) male (59.7%). Results: Although 35.3% of men and 44.4% of women remained in treatment for over a year, gender did not significantly predict treatment retention (X2(1) =2.47, p= .12). In the overall sample, Kendall correlations (dfs =282) revealed that presenting a urine sample positive for opiates, cocaine, or THC metabolites (rs = .29, .29, .24, respectively, all ps < .001) during the first month of treatment, having a DSM-IV diagnosis of cocaine dependence (r= .24, p