Transcriptional Mechanisms of Drug Addiction.

Transcriptional mechanisms of drug addiction.

Clin Psychopharmacol Neurosci. 2012 Dec; 10(3): 136-43
Nestler EJ

Regulation of gene expression is considered a plausible mechanism of drug addiction given the stability of behavioral abnormalities that define an addicted state. Numerous transcription factors, proteins that bind to regulatory regions of specific genes and thereby control levels of their expression, have been implicated in the addiction process over the past decade or two. Here we review the growing evidence for the role played by several prominent transcription factors, including a Fos family protein (?FosB), cAMP response element binding protein (CREB), and nuclear factor kappa B (NF?B), among several others, in drug addiction. As will be seen, each factor displays very different regulation by drugs of abuse within the brain’s reward circuitry, and in turn mediates distinct aspects of the addiction phenotype. Current efforts are geared toward understanding the range of target genes through which these transcription factors produce their functional effects and the underlying molecular mechanisms involved. This work promises to reveal fundamentally new insight into the molecular basis of addiction, which will contribute to improved diagnostic tests and therapeutics for addictive disorders. HubMed – addiction


Are Gambling Related Cognitions in Adolescence Multidimensional?: Factor Structure of the Gambling Related Cognitions Scale.

J Gambl Stud. 2013 Feb 21;
Taylor RN, Parker JD, Keefer KV, Kloosterman PH, Summerfeldt LJ

The present study examined the factor structure of the Gambling Related Cognitions Scale (GRCS); (Raylu and Oei in Addiction 99:757-769, 2004) in a large sample of adolescents (N = 1,490) between the ages of 16 and 18 years (630 males, 860 females) attending several high schools in central Ontario. Problem gambling was measured using the DSM-IV-J (Fisher in J Gambl Stud 8:263-285, 1992). A 5-factor GRCS model was found to have the best fit to the data, and gambling-related cognitions were found to be powerful predictors of disordered gambling among adolescents. However, strong associations among GRCS subscales, as well as the small amount of variance in problem gambling accounted for by specific GRCS subscales, call into question the multidimensionality of the GRCS when used with adolescents. HubMed – addiction


Iptakalim Preferentially Decreases Nicotine-induced Hyperlocomotion in Phencyclidine-sensitized Rats: A Potential Dual Action against Nicotine Addiction and Psychosis.

Clin Psychopharmacol Neurosci. 2012 Dec; 10(3): 168-79
Volf N, Hu G, Li M

Iptakalim is a putative ATP-sensitive potassium (K(ATP)) channel opener. It is also a novel nicotinic acetylcholine receptor (nAChR) blocker and can antagonize nicotine-induced increase in dopamine release in the nucleus accumbens. Our recent work also shows that iptakalim exhibits a clozapine-like atypical antipsychotic profile, indicating that iptakalim may possess a dual action against nicotine addiction and schizophrenia.The present study examined the potential therapeutic effects of iptakalim on nicotine use in schizophrenia. We created an animal model of comorbidity of nicotine addiction and schizophrenia by injecting male Sprague-Dawley rats with nicotine (0.40 mg/kg, subcutaneously[sc]) or saline, in combination with phencyclidine (PCP, 3.0 mg/kg, sc) or saline daily for 14 consecutive days.During the PCP/nicotine sensitization phase, PCP and nicotine independently increased motor activity over time. PCP also disrupted prepulse inhibition (PPI) of acoustic startle response. Acute nicotine treatment attenuated the PCP-induced hyperlocomotion and PCP-induced disruption of PPI, whereas repeated nicotine treatment potentiated these effects. Importantly, pretreatment with iptakalim (10-20 mg/kg, intraperitoneally) reduced nicotine-induced hyperlocomotion in a dose-dependent fashion. This reduction effect was highly selective: it was more effective in rats previously sensitized to the combination of PCP and nicotine, but less effective in rats sensitized to saline, nicotine alone or PCP alone.To the extent that the combined nicotine and PCP sensitization mimics comorbid nicotine addiction in schizophrenia, the preferential inhibitory effect of iptakalim on nicotine-induced hyperlocomotion suggests that iptakalim may be a potential useful drug for the treatment nicotine abuse in schizophrenia. HubMed – addiction


Which flap method should be preferred for the treatment of pilonidal sinus? A prospective randomized study.

Tech Coloproctol. 2013 Feb 21;
Arslan K, Said Kokcam S, Koksal H, Turan E, Atay A, Dogru O

BACKGROUND: Although many methods, either surgical or non-surgical, are being used for the treatment of pilonidal sinus disease (PSD), there is still no consensus as to what constitutes the most appropriate method of treatment. The aim of this study was to compare the outcomes of the Limberg flap (LF), modified Limberg flap (MLF), and Karydakis flap (KF) procedures. METHODS: A prospective, randomized study was conducted on 295 patients scheduled for surgical treatment for PSD at the General Surgery Clinic of the Konya Training and Research Hospital in January 2009-May 2010. Patients with recurrent disease, an ASA score higher than III, obesity (BMI > 35 kg/m(2)), insulin-dependent diabetes, or a drug or alcohol addiction were excluded. The procedures performed were as follows: LF (n = 96), MLF (n = 108), and KF (n = 91). RESULTS: The patients were followed up for a median of 33 months (range 24-41 months). There were more female patients in the LF group. The rate of seroma formation was higher in the KF group (19.8 %) compared to the LF and MLF groups (5.2 and 7.4 %, respectively; p = 0.027). The rate of wound dehiscence was higher in the KF group (15.4 %) compared to the LF and MLF groups (2.1 and 3.7 %, respectively; p < 0.001) as was the incidence of flap maceration (11 % in the KF vs. 1 % in the LF and 3.7 % in the MLF; p = 0.004). The incidence of PSD recurrence was also higher in the KF group (11 %) compared to the LF and MLF groups (6.3 and 1.9 % respectively; p = 0.027). In a multivariate analysis, the presence of seroma, hematoma, and wound infection were independent predictors of recurrence. CONCLUSIONS: In our study, LF and MLF procedures were associated with a lower recurrence and complication rate compared to KF. However, more randomized studies comparing different reconstruction methods after PSD excision are needed. HubMed – addiction



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