ELK1 Transcription Factor Linked to Dysregulated Striatal Mu Opioid Receptor Signaling Network and OPRM1 Polymorphism in Human Heroin Abusers.

ELK1 Transcription Factor Linked to Dysregulated Striatal Mu Opioid Receptor Signaling Network and OPRM1 Polymorphism in Human Heroin Abusers.

Biol Psychiatry. 2013 May 20;
Sillivan SE, Whittard JD, Jacobs MM, Ren Y, Mazloom AR, Caputi FF, Horvath M, Keller E, Ma’ayan A, Pan YX, Chiang LW, Hurd YL

BACKGROUND: Abuse of heroin and prescription opiate medications has grown to disturbing levels. Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. The striatum is a structure central to reward and habitual behavior and neurobiological changes in this region are thought to underlie the pathophysiology of addiction disorders. METHODS: We examined molecular mechanisms related to MOR in postmortem human brain striatal specimens from a homogenous European Caucasian population of heroin abusers and control subjects and in an animal model of heroin self-administration. Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history. RESULTS: A characteristic feature of heroin abusers was decreased expression of MOR and extracellular regulated kinase signaling networks, concomitant with dysregulation of the downstream transcription factor ELK1. Striatal ELK1 in heroin abusers associated with the polymorphism rs2075572 in OPRM1 in a genotype dose-dependent manner and correlated with documented history of heroin use, an effect reproduced in an animal model that emphasizes a direct relationship between repeated heroin exposure and ELK1 dysregulation. A central role of ELK1 was evidenced by an unbiased whole transcriptome microarray that revealed ~20% of downregulated genes in human heroin abusers are ELK1 targets. Using chromatin immune precipitation, we confirmed decreased ELK1 promoter occupancy of the target gene Use1. CONCLUSIONS: ELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1. HubMed – addiction


Effects of ethanol on immune response in the brain: region-specific changes in aged mice.

J Neuroinflammation. 2013 May 23; 10(1): 66
Kane CJ, Phelan KD, Douglas JC, Wagoner G, Johnson JW, Xu J, Drew PD

BACKGROUND: Alcohol abuse has dramatic effects on the health of the elderly. Recent studies indicate that ethanol increases immune activity in younger animals and that some of these proinflammatory molecules alter alcohol consumption and addiction. However, the effects of alcohol on immune activation in aged animals have not been thoroughly investigated. FINDINGS: We compared the effects of ethanol on chemokine and cytokine expression in the hippocampus, cerebellum, and cerebral cortex of aged C57BL/6 mice. Mice were treated via gavage with 6 g/kg ethanol for 10 days and tissue was harvested 1 day post-treatment. Ethanol selectively increased mRNA levels of the chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 in the hippocampus and cerebellum, but not in the cortex of aged mice relative to control animals. In this paradigm, ethanol did not affect mRNA levels of the cytokines IL-6 or TNF-alpha in any of these brain regions in aged animals. CONCLUSIONS: Collectively, these data indicate a region-specific susceptibility to ethanol regulation of neuroinflammatory and addiction-related molecules in aged mice. These studies could have important implications concerning alcohol-induced neuropathology and alcohol addiction in the elderly. HubMed – addiction


Analysis of refill liquids for electronic cigarettes.

Addiction. 2013 May 23;
Etter JF, Zäther E, Svensson S

AIMS: To assess levels of nicotine, nicotine degradation products and some specific impurities in commercial refill liquids for electronic cigarettes. DESIGN AND SETTING: We analyzed 20 models of 10 of the most popular brands of refill liquids, using gas and liquid chromatography. MEASUREMENTS: We assessed nicotine content, content of the known nicotine degradation products and impurities, and presence of ethylene glycol and diethylene glycol. FINDINGS: The nicotine content in the bottles corresponded closely to the labels on the bottles. The levels of nicotine degradation products represented 0-4.4% of those for nicotine, but for most samples the level was 1-2%. Cis-N-oxide, trans-N-oxide, myosmine, anatabine and anabasine were the most common additional compounds found. Neither ethylene glycol nor diethylene glycol were detected. CONCLUSION: The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in several brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm. HubMed – addiction


Realizing or Relinquishing Rights? Homeless Youth, Their Life on the Streets and Their Knowledge and Experience of Health and Social Services in Hillbrow, South Africa.

Soc Work Health Care. 2013 May-June; 52(5): 449-466
Mathebula SD, Ross E

Poverty and youth unemployment are critical issues in South Africa with homeless persons begging at traffic light intersections in all major cities. Support services represent one way of empowering homeless youth. The study therefore examined the experiences of 10 homeless young adult males in Hillbrow, Johannesburg and whether they were aware of local health and social services. Qualitative interviews revealed that participants experienced poor health, addiction, physical violence, psychological trauma, and public hostility. Despite limited education, they were aware of and utilized local health and social services. Findings are discussed in terms of their implications for social work. HubMed – addiction



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