The Role of G Protein In Alcohol Related Behaviours Using Drosophila melanogaster As A Model

Ethanol, classified as a drug, affects the central nervous system, and its consumption has been linked to the development of several behaviours including tolerance and dependence. Alcohol tolerance is defined as the need for higher doses of alcohol to induce the same changes observed in the initial exposure or where repetitive exposures of the same alcohol dose induce a lower response. Ethanol has been shown to interact with numerous targets and ultimately influence both short and long term adaptation at the cellular and molecular level in brain [1]. These adaptation processes are likely to involve signalling molecules: our work has focussed on G proteins gene expression. Using both wild type and several mutant fruit fly (Drosophila melanogaster) as a model for behaviour and molecular studies, we observed significant increases in sedation time (ST50) in response to alcohol (P<0.001) Fig.A. We also observed a consistent and significant decrease of Gq protein mRNA expression in Drosophila dUNC and DopR2 mutants chronically exposed to alcohol (*P<0.05). Fig B. Method: Six male flies were observed in drosophila polystyrene 25 x 95mm transparent vial in between cotton plugs. To the top plug, 500uL of 100% ethanol was added. Time till 50% of the flies were sedated was recorded on each day following the schedule. Fig. C (n=4-6). Using RT-PCR, we also quantified G protein mRNA expression levels one hour post initial 30 minutes of ethanol expression on day 1 and day 3 relative to expression in naïve flies.(n=2) [A] Increase in sedation time indicative of tolerance in different mutant lines and wild type flies. Six male flies were used in each experiment and (n= 4-6. ***P<0.001 unpaired t tests). [B] RT-PCR results showing significant reduction in Gq mRNA in flies chronically exposed to alcohol. (n=2. *P<0.05) [C] Alcohol exposure schedule. (1) Kaun K.R., R. Azanchi, Z. Maung, J. Hirsh, U. Heberlein. (2011). A Drosophila model for alcohol reward. Nature Neuroscience. 14 (5), 612–619.

The Well London program - a cluster randomized trial of community engagement for improving health behaviors and mental wellbeing: baseline survey results

Background The Well London programme used community engagement, complemented by changes to the physical and social neighbourhood environment, to improve physical activity levels, healthy eating and mental wellbeing in the most deprived communities in London. The effectiveness of Well London is being evaluated in a pair-matched cluster randomised trial (CRT). The baseline survey data are reported here. Methods The CRT involved 20 matched pairs of intervention and control communities (defined as UK census lower super output areas; ranked in the 11% most deprived LSOAs in London by Index of Multiple Deprivation) across 20 London boroughs. The primary trial outcomes, sociodemographic information and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline: a cross-sectional, interviewer-administered adult household survey; a self-completed, school-based adolescent questionnaire; a fieldworker completed neighbourhood environmental audit. Baseline data collection occurred in 2008. Physical activity, healthy eating and mental wellbeing were assessed using standardised, validated questionnaire tools. Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys. Results There were 4107 adults and 1214 adolescent respondents in the baseline surveys. The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics. The environmental characteristics of the intervention and control neighbourhoods were broadly similar. There was greater between cluster variation in the primary outcomes in the adult population compared to the adolescent population. Levels of healthy eating, smoking and self-reported anxiety/depression were similar in the Well London population and the national Health Survey for England. Levels of physical activity were higher in the Well London population but this is likely to be due to the different measurement tools used in the two surveys. Conclusions Randomisation of social interventions such as Well London is acceptable and feasible and in this study the intervention and control arms are well balanced with respect to the primary outcomes and key sociodemographic characteristics. The matched design has improved the statistical efficiency of the study amongst adults but less so amongst adolescents. Follow-up data collection will be completed 2012.