Objective To search for novel compounds with selective agonist activity at d-opioid receptors by screening cDNA libraries from skin of several frog speciesTo develop mice deficient in d-opioid receptors using the 'knockout technique' and by treatment with antisense oligonucleotides directed to the d-opioid receptorTo assess the role of d-opioid receptors in pain and drug addiction by behavioural, neuroanatomical and biochemical studies in normal and d-opioid receptor deficient animals The cloning of the d-opioid receptor and the discovery of selective compounds which act at this site has provided the opportunity to study the role of this receptor in the regulation of brain function and to assess the potential therapeutic importance of new compounds acting at this receptor in the treatment of pain and in drug addiction. The primary objective of the proposed project is to determine the role of d-receptors in pain and in motivational and rewarding aspects of opioids which may be responsible for drug addiction. The work programme will involve the development of novel compounds which act at the d-receptor by screening of cDNA libraries from frog skin, an approach which has previously been successful in obtaining highly selective tools active at the d-receptor. Using these and other d-agonists and antagonists, which have recently become available, behavioural studies, brain imaging of receptor proteins and mRNA encoding for the d-receptor, plus microdialysis techniques will be used to study d-receptor mediated changes in neurotransmitter release. To further probe the role of d-receptors, mutant 'knockout mice', deficient in d-opioid receptors, will be developed and treatments with antisense oligonucleotides directed to the d-receptor plus chronic antagonist treatment during development will be used to address the changes that occur in pain and in addictive processes in animals whose d-receptors have been disabled. These multidisciplinary approaches will allow evaluation of the physiological role of d-receptors in specific brain functions and will enable a clear delineation of a potential clinical utilisation of d-receptor active drugs. Throughout the work programme, using the novel tools outlined above, the issue of whether subtypes of the d-receptor exist and make a distinct contribution to pain suppression and addictive mechanisms will be addressed. The project will enhance our understanding of the role of d-receptors in pain and provide, by the discovery of novel d-opioid receptor peptides, potential new therapies for pain. It will also increase our understanding of the biological effects of illicit drugs on the structure and function of the brain by identifying the role of d-opioid receptors in dependence producing mechanisms. The project will also be using state of the art imaging techniques to map receptors and their genetic message in structures in the brain. Fields of science social sciencespsychologybehavioural psychologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Topic(s) 3.7 - Pain regulation and relief Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator University of Surrey EU contribution No data Address University of Surrey GU2 5XH GUILDFORD United Kingdom See on map Total cost No data Participants (6) Sort alphabetically Sort by EU Contribution Expand all Collapse all Institut National de la Santé et de la Recherche Médicale France EU contribution No data Address 4,Avenue de l'Observatoire 75270 PARIS See on map Total cost No data UNIVERSITY OF CAGLIARI Italy EU contribution No data Address Via Ospedale, 72 09124 CAGLIARI See on map Total cost No data Universidad Complutense de Madrid Spain EU contribution No data Address Universidad Complutense de Madrid 28040 MADRID See on map Total cost No data Università degli Studi di Roma La Sapienza Italy EU contribution No data Address Piazzale Aldo Moro 5 00185 Roma See on map Total cost No data Université Louis Pasteur, Strasbourg 1 France EU contribution No data Address Boulevard Sebastien Brand 67400 ILLKIRCH See on map Total cost No data Österreichische Akademie der Wissenschaften Austria EU contribution No data Address 11,Billrothstrasse 5020 SALZBURG See on map Total cost No data
