Addiction Rehab: {Triangleup}FosB Differentially Modulates Nucleus Accumbens Direct and Indirect Pathway Function.

{triangleup}FosB differentially modulates nucleus accumbens direct and indirect pathway function.

Filed under: Addiction Rehab

Proc Natl Acad Sci U S A. 2013 Jan 14;
Grueter BA, Robison AJ, Neve RL, Nestler EJ, Malenka RC

Synaptic modifications in nucleus accumbens (NAc) medium spiny neurons (MSNs) play a key role in adaptive and pathological reward-dependent learning, including maladaptive responses involved in drug addiction. NAc MSNs participate in two parallel circuits, direct and indirect pathways that subserve distinct behavioral functions. Modification of NAc MSN synapses may occur in part via changes in the transcriptional potential of certain genes in a cell type-specific manner. The transcription factor FosB is one of the key proteins implicated in the gene expression changes in NAc caused by drugs of abuse, yet its effects on synaptic function in NAc MSNs are unknown. Here, we demonstrate that overexpression of FosB decreased excitatory synaptic strength and likely increased silent synapses onto D1 dopamine receptor-expressing direct pathway MSNs in both the NAc shell and core. In contrast, FosB likely decreased silent synapses onto NAc shell, but not core, D2 dopamine receptor-expressing indirect pathway MSNs. Analysis of NAc MSN dendritic spine morphology revealed that FosB increased the density of immature spines in D1 direct but not D2 indirect pathway MSNs. To determine the behavioral consequences of cell type-specific actions of FosB, we selectively overexpressed FosB in D1 direct or D2 indirect MSNs in NAc in vivo and found that direct (but not indirect) pathway MSN expression enhances behavioral responses to cocaine. These results reveal that FosB in NAc differentially modulates synaptic properties and reward-related behaviors in a cell type- and subregion-specific fashion.
HubMed – addiction


Human carotid body neuroglobin, vascular endothelial growth factor and inducible nitric oxide synthase expression in heroin addiction.

Filed under: Addiction Rehab

Histol Histopathol. 2013 Jan 14;
Zara S, Porzionato A, De Colli M, Macchi V, Cataldi A, De Caro R, Di Giulio C

Aims: The carotid body (CB) represents the prime site for detecting and responding to hypoxia. Since the role of heroin in respiratory depression with consequent hypoxia is known, the authors were able to investigate morphological and molecular modifications occurring in the CB of heroin addicted subjects compared to subjects who died because of trauma. Methods and results: CB sampled from six 27 year old subjects, slides were treated with Mallory Trichrome staining or used for immunohistochemical analysis to detect neuroglobin (NGB), hypoxia inducible factor-1 (HIF-1?), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (i-NOS), Bax and cleaved caspase-3 proteins. Mallory Trichrome staining shows an increase in the connective tissue in heroin subjects compared to controls and a parallel reduction in parenchymal area. Immunohistochemical analyses in heroin subjects found a decrease in NGB and an increase in HIF-1? and VEGF compared to controls; i-NOS expression was not statistically significant. Bax and cleaved caspase-3 were positive only in the heroin subjects. Conclusions: These results could confirm the typical hypoxic condition occurring in heroin addicts. Since NGB may function as a reactive oxygen or nitrogen species scavenger and as apoptotic cell death protector, the decrease in its expression may suggest a key role of this globin in human CB impairment due to heroin addiction.
HubMed – addiction


High correlations between levels of consumption and mortality related to strong prescription opioid analgesics in British Columbia and Ontario, 2005 – 2009.

Filed under: Addiction Rehab

Pharmacoepidemiol Drug Saf. 2013 Jan 14;
Fischer B, Jones W, Rehm J

PURPOSE: Prescription opioid analgesic (POA)-related burden of disease – including mortality – is high and constitutes a major public health problem in the US and Canada. Associations between the overall levels of POA consumption and key related morbidity indicators in the population have been demonstrated. We examined potential correlations between levels of consumption of four commonly used POAs and related mortality in British Columbia (BC) and Ontario. METHODS: We investigated the correlation between annual population standardized rates of fentanyl, hydromorphone, morphine and oxycodone-related mortality (based on provincial coroners’ data) and the annual Defined Daily Doses per 1000 population/day for each of the drugs dispensed (based on representative retail pharmacy sales data) in the two provinces, 2005-2009. RESULTS: Death rates increased for three (Ontario) and two (BC) of the four POA drugs; the rate of deaths for each POA drug was consistently higher in the jurisdiction with higher use levels. For each drug, strong correlations (range 0.83 to 0.97; p?HubMed – addiction


The Effects of Age and Drug Dependency on the Emotional Exhaustion and Job Satisfaction of Adult Streetworkers in Australia.

Filed under: Addiction Rehab

Arch Sex Behav. 2013 Jan 15;
Cregan C, Kulik CT, Salinger D

This multi-method study investigated a sample of adult streetworkers (n = 107) in Melbourne, Australia in 2008. We contacted outdoor prostitutes through four “drop-in” centers run by not-for-profit organizations. Drug use was the over-riding common characteristic of most of these streetworkers. Using emotional labor theory as a theoretical framework, we hypothesized that individuals who worked on the streets solely to earn money to buy drugs would experience the highest levels of emotional exhaustion and the lowest levels of job satisfaction. We predicted these effects would be most evident for older drug dependent streetworkers. Content analysis of open-ended interview responses identified acting, age, and drug dependency as key themes. Moderator hierarchical regression analysis of responses to closed-ended questions with tests for mediation supported the hypotheses. It also demonstrated that older drug dependent streetworkers felt most trapped in their occupation and this sense of being locked-in was associated with emotional exhaustion but not with job satisfaction. The evidence that age and drug dependency affects the psychological outcomes associated with streetwork suggests that the efforts of police and the courts will be ineffective in dealing with people whose addiction traps them in an occupation that offers few intrinsic rewards. Decriminalization would encourage police to protect streetworkers from violence. Agencies could seek financial support to provide welfare and exit strategies.
HubMed – addiction



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