ALCOBINGE Management meeting report 14 April 2010

Transcription

1 ALCOBINGE Management meeting report 14 April 2010 Contents PARTICIPANTS... 2 MINUTES... 3 FEEDBACK FROM INTERREG MEETING... 3 WEB SITE... 3 AUDIT... 3 RECRUITMENT... 3 CONSIDERATIONS FOR HUMAN STUDIES... 4 CONSIDERATIONS FOR ANIMAL STUDIES... 4 CONSIDERATIONS FOR MOLECULAR STUDIES... 5 EXPERIMENTAL FINDINGS FROM PREVIOUS EXPERIMENTS/CURRENT RESEARCH INTERESTS THAT AFFECT THIS PROJECT... 5 FUTURE MEETINGS... 5

2 PARTICIPANTS 2 Mickaël Naassila : mickael.naassila@sa.u-picardie.fr Olivier Pierrefiche: olivier.pierrefiche@u-picardie.fr Harold Mouras: hmouras@gmail.com David Vaudry: david.vaudry@univ-rouen.fr Yacine Nekrouf: nekroufyacine@yahoo.fr Dai Stephens: D.Stephens@sussex.ac.uk Dora Duka : T.Duka@sussex.ac.uk Lynne Mayne: L.Mayne@sussex.ac.uk Tamzin Ripley: T.L.Ripley@sussex.ac.uk

3 MINUTES FEEDBACK FROM INTERREG MEETING MN reported back on his meeting with Interreg. Interreg were interested in how we would approach aspects of prevention of Alcohol Binging in the general population. Ways in which our results could be communicated to the general public and policy makers were discussed. 1. Powerpoint presentation could be prepared for the general public and for specific target audiences. DV already in a position to disseminate information through an educational program. 2. A Centre of Addiction Research is being developed at the University of Sussex reflecting its expertise in this area. This Centre will disseminate information to the UK Health Service and Educational Services. 3. The University of Sussex runs an MSc in Substance Misuse which provides a theoretical background for individuals working in the drug addiction field. Findings from the Alcobinge project will be disseminated through this course. 4. MN is the leader of a regional task force on alcoholism which is able to offer prevention initiatives including courses for physicians, professional drug workers, companies and the general population. Separate information will be designed to target younger age groups through to University students. N.B. All presentations and documentation needs to include the Interreg Logo including the EU logo (priority to the EU logo web site ) 3 WEB SITE DV has purchased the web site, which will now be our official home site. YN will be available to assist with the set up of this site. This site will include a News section where events that include the dissemination of information are posted, making final reporting of activities much easier. AUDIT The first claim period will be December All information needs to be with MN at the end of September RECRUITMENT 1. A project manager will be recruited by MN to work full time for 2.5 years to assist with the running of the grant and to help out with laboratory based project work. They will assist with financial aspects of the project, communication and organization of meetings. 2. A technician will also be recruited by MN to assist with the animal work. 3. A postdoctoral position will be provided by Amiens to support this work. This position will work on the Human Studies with TD and HM. Recruitment must be complete by December 2010, and the position will be for 1 year with a 1 year renewal. The salary

4 for this position is in line with French Postdoctoral salaries but is very low compared with UK postdocs ( 20,600 / yr). It was therefore felt that it would be best to recruit this individual from France. Ideal criteria for this position would include being bilingual, fmri experience, computing skills. 4. A technician/research assistant will be recruited in the UK to work on the animal and molecular biology studies. 4 CONSIDERATIONS FOR HUMAN STUDIES For the trans-channel Human Studies the following problems need to be overcome: 1. Recruitment of postdoc (see above) 2. Compatibility of French and UK imaging machine. At Sussex there is a 1.5T Magnetic Resonance (MR) imager. HM will look for a compatible machine in France. The Imagen project has experience of cross-centered fmri analysis, including morphing of images to fit a standard subject. Sussex has a Physicist associated with the scanner who may be able to help with this process. 3. Compatibility between EEG machines will be less of a problem as HM has a portable EEG machine that could be transported to the UK. 4. Ethical permission should be sorted out as soon as possible in France as it can take a long time to obtain. The postdoc could begin work in the UK where ethical approval is quicker. 5. CANTAB will need to be purchased in France as changes in Spatial Working Memory will need to be completed by all subjects. HM to chase this up as may be available. 6. Imagen project may be able to provide bilingual questionnaires, etc. 7. Additional tests of interest to HM should be included in the general test battery (e.g. empathy) 8. For follow-up studies we will need to consider the drop-out rate of University Students in France. TD suggested that given time constraints etc it might be better to only have a single scan for each student (or allow a smaller student sample to undergo follow-up fmri). CONSIDERATIONS FOR ANIMAL STUDIES It was decided that the binge protocol would be kept constant across all laboratories. The following points were decided: 1. DBA2J or C57Bl/6J mice will be used (note: C57Bl/6J mice should be purchased from Charles River to avoid α-synuclein deletion). 2. The binge procedure will consist of 2g/kg i.p., 2 days injection followed by 2 days withdrawal, 2 weeks chronic treatment period (total of 8 injections). The first injection should occur on PND30 (for early adolescence), PND45 (for late adolescence) or PND90 (for adulthood). 3. Still need to think about the duration of the final withdrawal period (i.e. period from last injection to start of experimental testing). 4. Will it be possible to look at hippocampal output (subiculum recordings) as these may be involved in context related relapse, and synaptic saturation? Synaptic saturation can also be tested in the CA1 field of the hippocampus.

5 CONSIDERATIONS FOR MOLECULAR STUDIES LM will focus on the very large mega base genes as these are enriched in neuronal functions and appear to have key roles in neuronal development and survival. Their extreme size suggests they will be vulnerable targets for DNA damage, such as reactive oxygen species, generated as a result of binge drinking. As their functions are intimately linked to roles such as neurotransmission and apoptosis and as alcohol induced DNA damage is likely to perturb gene transcription, many of the physiological and behavioural outcomes of binge drinking may be driven by changes in the expression of these genes. We will exploit Affymetrix Exon arrays and our extensive data base of very large gene structure, to measure the impact of alcohol on this subset of genes both at the transcriptional and RNA splicing level. DV is interest in looking a sensitivity of neurons to stroke damage following binge ethanol procedure, as well as damage induced by reactive oxygen species and effects on the neuropeptide PACAP. Experiments may need to look across the time course of binge exposure as alcohol-induced oxidative stress may alter across the treatment. 5 EXPERIMENTAL FINDINGS FROM PREVIOUS EXPERIMENTS/CURRENT RESEARCH INTERESTS THAT AFFECT THIS PROJECT MN: 2 day on/2 day off i.p. binge protocol during adolescence but not adulthood produces good results in the rat (3g/kg) including changes in motivation for ethanol (e.g. measured as changes in the Break-Point in operant self-administration tasks). This group is also currently running free-choice access using the escalation model and CPP. A similar protocol (daily i.p. injections of ethanol, 2 g/kg i.p.) produced locomotor sensitisation in DBA mice. Studies have also focused on immunohistochemical findings, including ieg; acetylation of histones and chromatic remodeling. OP: Synaptic plasticity in the hippocampus seems to be different throughout the binge procedure and is dependent upon the age of the animal during the treatment period. This result probably reflects the maturation of the hippocampal networks, which are thought to be fixed at 60 day. One aim of OP is to look at electrophysiological parameters in DBA mice that are insensitive to the sensitization procedure. TR: Long and short term changes in attentional processes following binge exposure to ethanol in C57Bl/6J mice using an injection binge protocol. DS: Extensive experience of impulsivity in mouse models through Imagen grant. TD: Extensive experience of all experimental techniques listed in the current grant, but new elements feature cross-cultural aspects, and population comparisons. LM: Interest in neuronal damage in mega-genes due to oxidative stress produced by alcohol. FUTURE MEETINGS A Management Meeting will take place every 6 months. The next meeting will take place in September 2010 at the ISBRA meeting in Paris. This will provide an opportunity to discuss any last minute information/evidence that needs to be included in the first payment claim.

6 Additional and more frequent meetings will be organized to talk about the science aspects of the project. 6