Neuronal Development Genes Are Key Elements Mediating the Reinforcing Effects of Methamphetamine, Amphetamine, and Methylphenidate.

Neuronal development genes are key elements mediating the reinforcing effects of methamphetamine, amphetamine, and methylphenidate.

Psychopharmacology (Berl). 2013 Jun 20;
Dela Peña I, Jeon SJ, Lee E, Ryu JH, Shin CY, Noh M, Cheong JH

RATIONALE: The molecular mechanisms underlying susceptibility to psychostimulant addiction remain unclear. Searching for commonalities in the effects of addictive drugs on brain gene expression is a prolific approach to determine transcriptional signatures influencing drug abuse. OBJECTIVE: We explored the common transcriptional responses to the reinforcing effects of psychostimulants methamphetamine, amphetamine, and methylphenidate. We also aimed to identify transcriptional changes that may subserve abuse of these drugs. METHODS: Genome-wide transcriptome profiling analyses were performed to identify common prefrontal cortical (PFC) and striatal gene expression profiles in drug-naïve (cohort 1) and stimulant-pretreated (cohort 2) rats, which showed a conditioned place preference to and self-administration of methamphetamine, amphetamine, and methylphenidate. RESULTS: In behavioral studies, stimulant-pretreated rats showed behavioral sensitization characterized by enhanced behavioral response to the rewarding or reinforcing effects of psychostimulants. Inflammation-associated genes (e.g., Alas1, S100a8 and S100a9) were identified as the primary differentially expressed genes (DEGs) in both the PFC and the striatum of cohort 1 rats, while neuronal plasticity (Sgk1)- and brain development (e.g., Bhlhe22, Neurod1, Nr4a2, and Msx1)-associated genes comprised the major upregulated DEGs in the striatum of cohort 2 rats. Furthermore, a meta-analysis of the common striatal DEGs in this study along with morphine-regulated striatal transcriptomes in mice (National Center for Biotechnology Information-Gene Expression Omnibus Database Accession Code GSE7762) suggested similar expression profiles of genes involved in neuronal development (e.g., Bhlhe22, Nr4a2). CONCLUSION: This study provides evidence that brain development-associated genes mediate the reinforcing effects of methamphetamine, amphetamine, and methylphenidate and that these transcripts may underlie susceptibility to psychostimulant addiction. HubMed – addiction


Dependence measures for non-cigarette tobacco products within the context of the global epidemic: a systematic review.

Tob Control. 2013 Jun 19;
De Leon E, Smith KC, Cohen JE

OBJECTIVES: Validated metrics of tobacco dependence exist, but their value for global surveillance of tobacco dependence and development of tobacco control interventions is not well understood. This paper reviews tobacco dependence metrics for non-cigarette products, and whether measures of tobacco dependence have been validated in low-income and middle-income countries (LMIC). DATA SOURCES: Searches were conducted in PubMed, Scopus, PsycINFO, EMBASE, CINAHL and Global Health databases using variant terms for types of tobacco, dependence, measures and validity/reliability. Articles discussing dependence theories and/or metrics were fully reviewed and synthesised. STUDY SELECTION: Searches yielded 2702 unique articles. Two independent coders identified 587 articles for abstract review, and 229 were subsequently fully reviewed. Findings from 50 eligible papers are summarised. DATA EXTRACTION: An initial thematic analysis concentrated on four concepts: general tobacco dependence, dependence metrics, tobacco dependence in LMIC and dependence on non-cigarette tobacco. DATA SYNTHESIS: Analysis identified 14 distinct tobacco dependence instruments. Existing metrics treat tobacco dependence as multifaceted. Measures have been developed almost exclusively around cigarette smoking, although some validation and application across products has occurred. Where cross-national validation has occurred, however, this has rarely included LMIC. CONCLUSIONS: For purposes of global surveillance of tobacco dependence, there is a compelling need for validated measures to apply universally across social contexts and a multitude of tobacco products. Alternatively, effective tobacco control interventions require validated dependence measures that integrate specific behavioural elements and social context of product use. While different measures of dependence are required to fulfil each of these goals, both have value in addressing the global tobacco epidemic. HubMed – addiction


Placental miRNA expression profiles associated with measures of infant neurobehavioral outcomes.

Pediatr Res. 2013 Jun 19;
Maccani MA, Padbury JF, Lester BM, Knopik VS, Marsit CJ

Background:A growing body of research suggests that the intrauterine environment influences fetal neurodevelopment by altering the functional placental epigenome. A number of miRNAs are expressed in the placenta, may be sensitive to dysregulation by environmental exposures, and are associated with adverse pregnancy outcomes. Our study aimed to identify relationships between placental miRNA expression and newborn neurobehavior.Methods:We examined the association between the expression of miR-16, miR-21, miR-93, miR-135b, miR-146a, and miR-182 in total RNA from the placentas of 86 term infants asmeasured by quantitative real-time PCR and newborn neurobehavioral outcomes as assessed using the NICU Network Neurobehavioral Scales (NNNS).Results:Bivariate analysis revealed that placental miR-16 expression is negatively associated with attention score (p=0.006), while expression of miR-146aand miR-182 are both positively associated with quality of movement score (p=0.016 and p=0.016, respectively). Controlling for potential confounders, high miR-16 expression is significantly associated with reduced attention score (p=0.04), and high miR-146a expression and high miR-182 expression are significantly associated with increased quality of movement score (p=0.04 and p=0.01, respectively).Conclusions:These results suggest that placental miRNA expression is associated with early neurobehavioral outcomes and miRNAs in the placenta may contribute to the developmental origins of infant neurobehavior.Pediatric Research (2013); doi:10.1038/pr.2013.102. HubMed – addiction


An alcohol-focused intervention versus a healthy living intervention for problem drinkers identified in a general hospital setting (ADAPTA): study protocol for a randomized, controlled pilot trial.

Trials. 2013 Apr 30; 14(1): 117
Watson J, Tober G, Raistrick D, Mdege N, Dale V, Crosby H, Godfrey C, Lloyd C, Toner P, Parrott S

BACKGROUND: Alcohol misuse is a major cause of premature mortality and ill health. Although there is a high prevalence of alcohol problems among patients presenting to general hospital, many of these people are not help seekers and do not engage in specialist treatment. Hospital admission is an opportunity to steer people towards specialist treatment, which can reduce health-care utilization and costs to the public sector and produce substantial individual health and social benefits. Alcohol misuse is associated with other lifestyle problems, which are amenable to intervention. It has been suggested that the development of a healthy or balanced lifestyle is potentially beneficial for reducing or abstaining from alcohol use, and relapse prevention. The aim of the study is to test whether or not the offer of a choice of health-related lifestyle interventions is more acceptable, and therefore able to engage more problem drinkers in treatment, than an alcohol-focused intervention.Methods/design: This is a pragmatic, randomized, controlled, open pilot study in a UK general hospital setting with concurrent economic evaluation and a qualitative component. Potential participants are those admitted to hospital with a diagnosis likely to be responsive to addiction interventions who score equal to or more than 16 on the Alcohol Use Disorders Identification Test (AUDIT). The main purpose of this pilot study is to evaluate the acceptability of two sorts of interventions (healthy living related versus alcohol focused) to the participants and to assess the components and processes of the design. Qualitative research will be undertaken to explore acceptability and the impact of the approach, assessment, recruitment and intervention on trial participants and non-participants. The effectiveness of the two treatments will be compared at 6 months using AUDIT scores as the primary outcome measure. There will be additional economic, qualitative and secondary outcome measurements. DISCUSSION: Development of the study was a collaboration between academics, commissioners and clinicians in general hospital and addiction services, made possible by the Collaboration in Leadership in Applied Health Research and Care (CLAHRC) program of research. CLAHRC was a necessary vehicle for overcoming the barriers to answering an important NHS question — how better to engage problem drinkers in a hospital setting.Trial registration: ISRCTN47728072. HubMed – addiction


The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview.

Curr Pharm Des. 2013 Jun 14;
Martinotti G, Lupi M, Sarchione F, Santacroce R, Salone A, De Berardis D, Serroni N, Cavuto M, Signorelli M, Aguglia E, Valchera A, Iasevoli F, Di Giannantonio M

Pregabalin is an anticonvulsant drug that binds to the ?2? (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases. HubMed – addiction