MicroRNAs and Drug Addiction.

MicroRNAs and Drug Addiction.

Front Genet. 2013; 4: 43
Bali P, Kenny PJ

Drug addiction is considered a disorder of neuroplasticity in brain reward and cognition systems resulting from aberrant activation of gene expression programs in response to prolonged drug consumption. Non-coding RNAs (ncRNAs) are key regulators of almost all aspects of cellular physiology. MicroRNAs (miRNAs) are small (?21-23 nucleotides) ncRNAs transcripts that regulate gene expression at the post-transcriptional level. Recently, miRNAs were shown to play key roles in the drug-induced remodeling of brain reward systems that likely drives the emergence of addiction. Here, we review evidence suggesting that one particular miRNA, miR-212, plays a particularly prominent role in vulnerability to cocaine addiction. We review evidence showing that miR-212 expression is increased in the dorsal striatum of rats that show compulsive-like cocaine-taking behaviors. Increases in miR-212 expression appear to protect against cocaine addiction, as virus-mediated striatal miR-212 overexpression decreases cocaine consumption in rats. Conversely, disruption of striatal miR-212 signaling using an antisense oligonucleotide increases cocaine intake. We also review data that identify two mechanisms by which miR-212 may regulate cocaine intake. First, miR-212 has been shown to amplify striatal cAMP response element binding protein (CREB) signaling through a mechanism involving activation of Raf1 kinase. Second, miR-212 was also shown to regulate cocaine intake by repressing striatal expression of methyl CpG binding protein 2 (MeCP2), consequently decreasing protein levels of brain-derived neurotrophic factor (BDNF). The concerted actions of miR-212 on striatal CREB and MeCP2/BDNF activity greatly attenuate the motivational effects of cocaine. These findings highlight the unique role for miRNAs in simultaneously controlling multiple signaling cascades implicated in addiction. HubMed – addiction


Addiction and seizure ability of tramadol in high-risk patients.

Indian J Anaesth. 2013 Jan; 57(1): 86-7
Mehrpour O

HubMed – addiction


Establishing disability weights from pairwise comparisons for a US burden of disease study.

Int J Methods Psychiatr Res. 2013 May 28;
Rehm J, Frick U

To determine valid and reliable disability weights for a U.S. burden of disease study, a convenience sample of 68 clinical experts was recruited, including representatives from over 20 NIH institutes and Centers for Disease Control and Prevention. Experts were given various health state valuation tasks including pairwise comparison, ranking, and Person Trade Off. Materials consisted of standardized descriptions of 11 attributes per health state (Classification and Measurement System of Functional Health, CLAMES). Attributes comprised up to 5 ordinal levels of disability. All states were displayed either with or without health state labels. Health state descriptions were taken from an existing comprehensive Canadian system. Conditional Logistic (CLR) and Probit Regression (PR) were used to derive disability weights. CLR and PR converged in yielding stable regression weights to construct disability weights, with a correlation of 0.816. The overall test-retest reliability amounted to 92.5% identical decisions. No significant difference was found for the presentation of health states with or without labels. A comparison of the expert valuations from our study with a standard gamble based valuation in the general population resulted in agreement of r = 0.61. The chosen methodology yielded valid and reliable and disability weights. As it is based on a modularized set of attributes, this methodology will allow derivation of disability weights on the basis of existing descriptions using the CLAMES. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – addiction


Dopamine transporter availability in heroin-dependent subjects and controls: longitudinal changes during abstinence and the effects of Jitai tablets treatment.

Psychopharmacology (Berl). 2013 May 29;
Liu Y, Han M, Liu X, Deng Y, Li Y, Yuan J, Lv R, Wang Y, Zhang G, Gao J

RATIONALE: Previous imaging studies have indicated that the levels of the dopamine transporter (DAT) are reduced in the brains of heroin users. However, whether these changes can be reversed by abstinence and/or treatment remains unclear. OBJECTIVES: This study aims to investigate DAT availability in heroin users and changes in DAT availability after abstinence and treatment with the Jitai tablets, a traditional Chinese medicinal product that is approved for the treatment of opioid addiction. METHODS: Single-photon emission computed tomography (SPECT) with [(99m)Tc] TRODAT-1 was performed on heroin-dependent patients (n?=?64) and healthy controls (n?=?15). The patients were randomly assigned to treatment with either placebo or the Jitai. All patients underwent SPECT imaging both at baseline and after 6 months of treatment. DAT availability was assessed in the caudate and putamen. Depression and anxiety were evaluated at baseline. RESULTS: DAT availability remained at low levels during a 6-month period in the placebo-treated group but was increased (14-17 %) in the Jitai-treated group. The ratio of DAT availability at month 6 to that at baseline in the Jitai-treated group was significantly higher than that in the placebo-treated group in both the bilateral caudate and putamen. DAT uptake in the striatum was significantly correlated with daily heroin dose, years of heroin use, and depression. CONCLUSIONS: These findings suggest that chronic heroin use induces long-lasting striatal DAT reductions. DAT availability remained unchanged during a 6-month period of abstinence. Treatment with Jitai appears to be effective at increasing striatal DAT availability. HubMed – addiction


Effects of the Opioid Receptor Antagonist Naltrexone on Smoking and Related Behaviors in Smokers Preparing to Quit: A Randomized Controlled Trial.

Addiction. 2013 May 28;
King A, Cao D, Zhang L, Rueger SY

AIMS: To determine if naltrexone affects smoking behaviours in smokers preparing to quit, and whether such pre-quit responses predict post-quit date outcomes. DESIGN: Double-blind, placebo-controlled, randomized study. Current study focused on smoking-related outcomes in the pre-quit phase, which was one week prior to the quit date, and these findings were linked with reductions in same outcomes demonstrated in the post-quit phase previously published for this RCT in mediation analyses. SETTING: Community sample of adult smokers desiring to quit in Chicago, Illinois USA. PARTICIPANTS: Participants were 315 smokers randomized to naltrexone (n=161; mean age=42.6 years; 60% white) or placebo (n=154; mean age=41.3 years; 55% white). MEASUREMENTS: Difference from baseline in the number of cigarettes smoked during pre-quit phase interval was the primary outcome. Secondary pre-quit outcomes were assessed using Likert scales of subjective responses and consumption of cigarettes, alcohol, and food. Number of cigarettes smoked, alcoholic drinks consumed, and the Brief Questionnaire of Smoking Urges were assessed in the post-quit phase. FINDINGS: Relative to placebo, naltrexone decreased the number of cigarettes smoked (-4.21 vs. -2.93, p<.05), smoking urge (p=.02), and number of alcoholic drinks consumed (p=.04). Exploratory mediation analyses linking outcomes of the pre quit and post quit phases found that naltrexone's effects on reducing smoking urge, cigarettes smoked and alcoholic drinks consumed in the pre-quit phase demonstrated full mediation of their respective effects during the post-quit phase. CONCLUSIONS: Naltrexone taken in the week before a quit attempt appears to reduce cigarette consumption, urges to smoke and alcohol consumption relative to placebo. The size of the effect statistically mediates the size of similar effects after the quit date. HubMed – addiction