Addiction Rehab: Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking.

Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking.

Filed under: Addiction Rehab

Nicotine Tob Res. 2012 Dec 13;
Shao XM, Xu B, Liang J, Xie XS, Zhu Y, Feldman JL

INTRODUCTION: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. METHODS: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. RESULTS: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2±15.7ng/ml (mean ± SD) within 1-4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC(50) = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. CONCLUSIONS: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics.
HubMed – addiction


Searching for truth: internet search patterns as a method of investigating online responses to a Russian illicit drug policy debate.

Filed under: Addiction Rehab

J Med Internet Res. 2012; 14(6): e165
Zheluk A, Gillespie JA, Quinn C

This is a methodological study investigating the online responses to a national debate over an important health and social problem in Russia. Russia is the largest Internet market in Europe, exceeding Germany in the absolute number of users. However, Russia is unusual in that the main search provider is not Google, but Yandex.This study had two main objectives. First, to validate Yandex search patterns against those provided by Google, and second, to test this method’s adequacy for investigating online interest in a 2010 national debate over Russian illicit drug policy. We hoped to learn what search patterns and specific search terms could reveal about the relative importance and geographic distribution of interest in this debate.A national drug debate, centering on the anti-drug campaigner Egor Bychkov, was one of the main Russian domestic news events of 2010. Public interest in this episode was accompanied by increased Internet search. First, we measured the search patterns for 13 search terms related to the Bychkov episode and concurrent domestic events by extracting data from Google Insights for Search (GIFS) and Yandex WordStat (YaW). We conducted Spearman Rank Correlation of GIFS and YaW search data series. Second, we coded all 420 primary posts from Bychkov’s personal blog between March 2010 and March 2012 to identify the main themes. Third, we compared GIFS and Yandex policies concerning the public release of search volume data. Finally, we established the relationship between salient drug issues and the Bychkov episode.We found a consistent pattern of strong to moderate positive correlations between Google and Yandex for the terms “Egor Bychkov” (r(s) = 0.88, P < .001), "Bychkov" (r(s) = .78, P < .001) and "Khimki"(r(s) = 0.92, P < .001). Peak search volumes for the Bychkov episode were comparable to other prominent domestic political events during 2010. Monthly search counts were 146,689 for "Bychkov" and 48,084 for "Egor Bychkov", compared to 53,403 for "Khimki" in Yandex. We found Google potentially provides timely search results, whereas Yandex provides more accurate geographic localization. The correlation was moderate to strong between search terms representing the Bychkov episode and terms representing salient drug issues in Yandex-"illicit drug treatment" (r(s) = .90, P < .001), "illicit drugs" (r(s) = .76, P < .001), and "drug addiction" (r(s) = .74, P < .001). Google correlations were weaker or absent-"illicit drug treatment" (r(s) = .12, P = .58), "illicit drugs " (r(s) = -0.29, P = .17), and "drug addiction" (r(s) = .68, P < .001).This study contributes to the methodological literature on the analysis of search patterns for public health. This paper investigated the relationship between Google and Yandex, and contributed to the broader methods literature by highlighting both the potential and limitations of these two search providers. We believe that Yandex Wordstat is a potentially valuable, and underused data source for researchers working on Russian-related illicit drug policy and other public health problems. The Russian Federation, with its large, geographically dispersed, and politically engaged online population presents unique opportunities for studying the evolving influence of the Internet on politics and policy, using low cost methods resilient against potential increases in censorship. HubMed – addiction


Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction.

Filed under: Addiction Rehab

Pharmacol Rep. 2012 Sep; 64(5): 1126-34
Grzywacz A, Jasiewicz A, Ma?ecka I, Suchanecka A, Grochans E, Karakiewicz B, Samochowiec A, Bie?kowski P, Samochowiec J

Background: We investigated the relationship between withdrawal syndrome symptoms and dopamine receptor 2 DRD2 gene polymorphisms-141 C I/D (rs1799732) exon 8 G/A (rs6276) and ANKK1 (Ankyrin Repeat and Kinase Domain Containing 1) gene polymorphism Taq1A (rs1800497). Material: A total number of 213 patients who met the ICD 10 criteria for given phenotypes were enrolled in the study. Those phenotypes included: dissocial personality disorder, early onset, alcohol withdrawal syndrome with seizures, alcohol withdrawal syndrome with delirium tremens, and alcohol withdrawal syndrome with seizures and delirium tremens. Results: Our results show statistically significant associations between SNP in exon 8 A/G in the DRD2 gene and alcohol withdrawal syndrome with seizures, and between SNP in promoter -141 C I/D in the DRD2 gene and early onset of alcohol dependence (AD). The A/A genotype in exon 8 A/G polymorphism seems to be a positive predictive factor for the presence or the lack of seizures in alcohol withdrawal syndrome. The A/G genotype is possibly a protective factor for this AD phenotype. Conclusions: These results suggest that both investigated DRD2 polymorphisms have an impact on the AD phenotype. The findings of the presented study reconfirm that dopamine receptor 2 gene polymorphisms are associated with alcohol addiction and alcohol withdrawal syndrome.
HubMed – addiction


Effects of morphine on immediate-early gene expression in the striatum of C57BL/6J and DBA/2J mice.

Filed under: Addiction Rehab

Pharmacol Rep. 2012 Sep; 64(5): 1091-104
Zió?kowska B, Korosty?ski M, Piechota M, Kubik J, Przew?ocki R

Background: Immediate early gene (IEG) induction elicited by drugs of abuse may contribute to development of plastic changes in the brain responsible for drug-induced behavioral changes leading to addiction. The aim of the present study was to characterize the changes in IEG expression in the striatum and nucleus accumbens produced by an acute or chronic administration of morphine. Methods: In order to search for a possible relationship between morphine-induced IEG expression and behavior, the experiment was performed on two inbred strains of mice, C57BL/6J and DBA/2J, which differ markedly in their sensitivity to the rewarding and locomotor stimulatory actions of opiates. Gene expression was assessed using RT-PCR and DNA microarrays. Results: The experiments demonstrated a prolonged or a delayed up-regulation of 14 IEG in the striatum at 4 h after morphine administration. Among them, a cluster of 8 genes, including 6 inducible transcription factors (c-fos, fra-2, junB, zif268 (egr1), egr2, NGFI-B) and 2 effector IEG (arc and mkp1) seemed to be regulated in concert in response to morphine. This group of genes was induced to a greater degree after chronic than acute morphine administration selectively in C57BL/6J mice and the difference bore apparently no relationship to opiate-produced locomotor activation. The strain-selective regulation was also demonstrated for cyclin L2 and tPA after an acute morphine injection. Conclusions: Our data indicate that morphine up-regulates many IEG in the mouse striatum at a strikingly delayed time-point and that these changes are genotype-dependent. They also suggest inter-strain differences in the development of striatal neuroadaptations to chronic morphine treatment.
HubMed – addiction


Kinematic study on the effect of pH on bull sperm function.

Filed under: Addiction Rehab

Anim Reprod Sci. 2012 Nov 22;
Contri A, Gloria A, Robbe D, Valorz C, Wegher L, Carluccio A

Since the mammalian spermatozoa became capable of motion, during the epididymal transit, the spermatozoon swims in a liquid medium and it is completely dependent on the environmental conditions. Some reports have suggested an influence of pH on sperm kinetic characteristics, but no study has objectively described how motility changes in a different environmental pH. In this study, we evaluated the effect of different environmental pHs (5.5, 6, 6.5, 7, 7.5, 8, and 8.5) on kinetic parameters, sperm viability, mitochondrial activity, and sperm morphology of bull semen immediately and 1h after dilution. The results showed higher values for sperm motility characteristics, viability, and mitochondrial activity at pH 7 and 7.5. Values of pH lower than 6.5 and higher than 8 resulted in suboptimal motility, with a decrease in most parameters. At pH 8 and 8.5, a discrepancy between viability and total and progressive motility was found, with a significant amount of spermatozoa that were live but immotile. This reduction seemed related to a decrease in mitochondrial activity, possibly due to the increase in pH. The flow cytometric evaluation of sperm viability assessed by calcein AM was very consistent with the amount of spermatozoa with membrane integrity, evaluated in fluorescence by propidium iodide/SYBR-14 stain. Thus, the calcein AM stain could be used as viability stain instead the classic propidium iodide/SYBR-14 stain because this could allow the addiction of other functional stains without a overlapping of the fluorescent signal in the flow cytometer.
HubMed – addiction


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