Addiction Rehab: Morphine Epigenomically Regulates Behavior Through Alterations in Histone H3 Lysine 9 Dimethylation in the Nucleus Accumbens.

Morphine Epigenomically Regulates Behavior through Alterations in Histone H3 Lysine 9 Dimethylation in the Nucleus Accumbens.

Filed under: Addiction Rehab

J Neurosci. 2012 Nov 28; 32(48): 17454-64
Sun H, Maze I, Dietz DM, Scobie KN, Kennedy PJ, Damez-Werno D, Neve RL, Zachariou V, Shen L, Nestler EJ

Dysregulation of histone modifying enzymes has been associated with numerous psychiatric disorders. Alterations in G9a (Ehmt2), a histone methyltransferase that catalyzes the euchromatic dimethylation of histone H3 at lysine 9 (H3K9me2), has been implicated recently in mediating neural and behavioral plasticity in response to chronic cocaine administration. Here, we show that chronic morphine, like cocaine, decreases G9a expression, and global levels of H3K9me2, in mouse nucleus accumbens (NAc), a key brain reward region. In contrast, levels of other histone methyltransferases or demethylases, or of other methylated histone marks, were not affected in NAc by chronic morphine. Through viral-mediated gene transfer and conditional mutagenesis, we found that overexpression of G9a in NAc opposes morphine reward and locomotor sensitization and concomitantly promotes analgesic tolerance and naloxone-precipitated withdrawal, whereas downregulation of G9a in NAc enhances locomotor sensitization and delays the development of analgesic tolerance. We identified downstream targets of G9a by providing a comprehensive chromatin immunoprecipitation followed by massively parallel sequencing analysis of H3K9me2 distribution in NAc in the absence and presence of chronic morphine. These data provide novel insight into the epigenomic regulation of H3K9me2 by chronic morphine and suggest novel chromatin-based mechanisms through which morphine-induced addictive-like behaviors arise.
HubMed – addiction


Convergent Effects of Acute Stress and Glucocorticoid Exposure upon MAO-A in Humans.

Filed under: Addiction Rehab

J Neurosci. 2012 Nov 28; 32(48): 17120-17127
Soliman A, Udemgba C, Fan I, Xu X, Miler L, Rusjan P, Houle S, Wilson AA, Pruessner J, Ou XM, Meyer JH

Monoamine oxidase-A (MAO-A), a key brain enzyme which metabolizes monoamines, is implicated in the pathophysiology of stress-related illnesses, including major depressive disorder, addiction, and violent behavior. Chronic stressors and glucocorticoid-administration typically associate with elevated MAO-A levels/activity. However, the relationship of shorter stress or glucocorticoid exposures and MAO-A levels/activity is not well established. Our objectives are to assess effects of acute stress upon MAO-A V(T,) an index of MAO-A density, in human brain and acute glucocorticoid exposure upon MAO-A levels in human neuronal and glial cell lines. Twelve healthy, non-smoking participants aged 18-50 underwent [(11)C]harmine positron emission tomography to measure brain MAO-A V(T) on two different days: One under acute psychosocial stress (via Trier Social Stress and Montreal Imaging Stress Tasks) and one under a non-stress condition. MAO-A density (by Western blot) and activity (by [(14)C]-5-HT metabolism and liquid scintillation spectroscopy) were measured in human neuronal and glial cell lines after 4 h exposure to dexamethasone. We observed a significant reduction in whole-brain MAO-A binding as reflected by reductions in 10 of 11 brain regions. Acute dexamethasone exposure in neuronal and glial cells significantly decreased MAO-A activity and protein levels. We observed a highly consistent relationship between acute stressors and glucocorticoid administration and decreased MAO-A binding, activity and protein levels. Since MAO-A metabolizes monoamines, this phenomenon may explain why acute stressors benefit healthy animals even though chronic stress is associated with illness.
HubMed – addiction


Enhanced care for depression.

Filed under: Addiction Rehab

Curr Opin Psychiatry. 2013 Jan; 26(1): 7-12
Beekman AT, Feltz-Cornelis CV, van Marwijk HW

The purpose of this study is to review recent evidence of the effects of enhanced depression care, focusing (1) on symptomatic, functional and economic outcomes and (2) across different countries, (3) ethnic groups and (4) settings.Collaborative care is currently by far the most influential and best studied method to enhance depression care. Recent trials and reviews provide firm evidence that collaborative care is more effective than care as usual (CAU), though with small effects. These effects generalized across several important health outcomes are probably more pronounced in patients with more complex or severe disorders. Cost-effectiveness and cost utility data demonstrate that collaborative care is of good value for money, and this is probably more pronounced in patients with higher a-priori levels of healthcare utilization. Collaborative care is readily exported to other healthcare systems, other regions of the world and other cultures.Given parallel development and successful testing of other cheaper and more simple interventions targeting depression (such as guided self-help and e-mental health), it may be that collaborative care will focus on the more severe, complex or recurrent forms of affective disorder in the future. Including effects of collaborative care on other outcomes, especially on work-related functioning and economic productivity, seems fruitful.
HubMed – addiction


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