Professor Maldonado is the partnership co-ordinator, encompassing behavioural studies and phenotypical characterisation of two animal models, owing to the large background of his group in the study of drug addictive processes.

In recent years, they have made a major contribution to the neurobiological mechanisms involved in these processes by using classical pharmacological approaches as well as several lines of knockout mice. Multiple behavioural techniques have been used in this context, including somatic and biochemical expression of withdrawal, place conditioning paradigm using standard and novel protocols, intravenous self-administration for studying acquisition, extinction and relapse of the operant behaviour, behavioural models of sensitization to locomotor and rewarding effects, behavioural models of anxiety and several models of depression.

Prof. Maldonado has extensive experience in participating in collaborative programmes (several European Commission 4th, 5th and 6th FP, Human Frontier Science and USA-NIH) and has been coordinator of two Biomed programmes (Biomed I and II) and one PECO programme of previous Framework programmes of the European Commission.

The group of Dr. Mara Dierssen (Genes and Disease Prog., Genomic Regulation Centre, CGR), develops projects of gene identification, generation of experimental models of human diseases, evaluation of behaviour in murine models of diseases, and gene transfer applications for the treatment of human disorders, including several neuropsychiatric diseases, e.g. anorexia nervosa, bulimia and compulsive overeating.

Using a wide variety of relevant behavioral paradigms, the laboratory of Mara is investigating specific links between cognitive impairments and memory disorders in patients with Down syndrome and behavioral deficits in mouse models of this disease. We are also currently working on candidate genes involved in dendrites/spine dysmorphology and altered neural plasticity in learning and memory brain circuits. Our second research line is directed to the study of panic disorder. We are interested in candidate genes that participate in the dysfunction of brain circuits involved in fear-related memories and in mouse behavioral traits relevant to panic and to anxiety.

Most of our work employs the use of transgenic and knockout mice for genes expressed in the brain, but we also obtain important information about the genetic basis of behavior performing inbred strain surveys and studying recombinant inbred strains. Our experimental approaches include behavioral analysis with multiple assessment tools that will detect basic alterations in nervous system function. Assessment targets are basic neurological function, brainstem-spinal cord reflex, motor function/control centers, exploratory activity, anxiety-related responses, depression, sensorimotor gating, social interactions, and learning and memory. We also use neurohistological and morphometric approaches to determine a structural correlation for the detected phenotypic traits and cellular/molecular biology techniques to get insight into the underlying mechanism

Professor Przewlocka will be responsible of themolecular studies, be a member of the steering group and oversee gender and ethical issues. Her team is one of the most experienced in opioid system physiology and pharmacology in Europe and has over 20 years experience in opioid pharmacology. Her work is focused on neuropharmacology, mainly on opioid effects in tolerance development.

Prof. Przewlocka and her co-operators were one of the first demonstrating the enhancement of dynorphin expression and effects of dynorphin and its analogs in the spinal cord upon chronic pain. Furthermore she demonstrated the expression of opioid peptides in the immune cells in inflamed tissue. More recently her scientific team has searched for genes in the nervous system regulated by opioids. This group accumulated data suggesting that opioids activate transcription factors and in consequence influence transcription of various genes. Recently, they search for genes with changed expression in behavioural models of morphine self-administration in rats.

More recently his scientific team has searched for genes in the nervous system regulated by opioids. The Polish participant has had European collaboration in the opioid area with some of the other EU partners in this bid as well as being a participant in a Framework V and VI grants.

Prof. Spanagel will be responsible of WP2 and he will be a member of the steering group, giving support to the co-ordinator in scientific/technical issues and overseeing education /training issues. He and his team are working for many years in the field of drug abuse

With their alcohol deprivation model they have made basic contributions to our understanding of compulsive drug-seeking and drug-taking behaviour. Although this model needs some refinements as outlined in this proposal (see WP2), it has already become a standard model in many laboratories around the world and the Spanagel team has published more than 30 papers using this rat model

What is more, new treatment strategies have evolved from these studies demonstrating the translational impact of this work. In parallel, Spanagel and his co-workers have been very successful in translating the rat work to new mouse models. Thus, using transgenic mice some key papers in the alcohol field could be accomplished and very recently the Spanagel team successfully set up the reinstatement paradigm in transgenic mice in order to measure cue-induced alcohol-seeking behaviour (craving) a model which has been translated for the first time to mice.

Dr. Piazza and his team have worked for years in the physiopathology of drug dependence. They have made major contributions in the elucidation of the neurobiological substrate of drug addiction and have set up and fully characterized in rat a model of compulsive drug intake, which now waits to be transferred to mice.

The whole group (INSERM U.588) currently operates methodologies for the evaluation of behaviour, namely memory, learning, anxiety, drug taking and circadian rhythm, for the evaluation of neuronal activity, such as in vivo microdialysis, neurotransmitter release, electrophysiology and functional anatomy, as well as in cellular and molecular biology (i.e. quantitative PCR, transgenesis, cloning).

Dr. Andrea Heyne will be responsible of WP4. She and Urte Dahm founded medimod in early 2003, medimod is a wholly privately owned science driven independent Contract Research Organization specialising in behavioural CNS pharmacology.

On behalf of their clients in the pharmaceutical industry, they support compound development by testing drug eficacy (CNS primary and secondary indications), drug safety (CNS side effects) and overall drug effects (screening for new compounds).

A. Heyne holds a PhD in biology, has more than 15 years of experience in behavioural pharmacology and is responsible for the scientific leadership of the company. U. Dahm has a degree in business administration and her focus is on finances and project management. Medimod's team consists of about 30 people, most of them behavioural biologists and technicians. medimod aims at establishing module-based standard of animal models for different CNS-indications. Their role in the project will be to carry out the behavioural and pharmacological characterisation of their compulsive food seeking/food taking model in rat.

Dr. Millán will be responsible of WP7 and of neuroimaging of small experimental animals, as well as member of the steering group, overseeing quality assurance and IPR issues. Institut d’Alta Tecnologia (IAT) is a non-profit private foundation focused on Molecular Imaging and located at the Parc de Recerca Biomèdica de Barcelona (PRBB). It was founded in April 2002 and started operating in Spring 2004.

The goal of this foundation is to act as a centre of reference in Molecular Imaging for the Spanish and European Scientific Community and Academia, by offering both positron technology and training. They are also likely to collaborate with the Pharmaceutical Industry both at a preclinical and at a clinical level in the development of new drugs. Its income for these services will more than double in 2005 with respect to 2004 (454 kfi) and permanent staff will increase twice in the same period. Among the existing Molecular Imaging techniques, IAT focuses on positron technology, as Positron Emission Tomography (PET) is a non-invasive technique that provides metabolic information at a molecular level in both animals and humans, and allows longitudinal and translational studies. It is also a highly specific technique, since radiolabelled molecules can be detected and quantified (even absolutely) from picomolar concentrations and allow the precise monitoring of their biodistribution, kinetics and metabolic effects.

At present, IAT counts with infrastructure for the production of radiotracers (a cyclotron and a fully equipped radiochemistry lab), and tomographs for the acquisition of PET images in both humans and small animals. IAT has also recruited a multidisciplinary and highly specialized young team, capable of approaching a wide range of research protocols involving PET imaging. This company will be responsible for the neuroimaging studies of rat and mice.

François Tronche will be the responsible of WP6. Dr. Tronche has been working for years on transcriptional regulation of gene expression. On leave from the CNRS, he joined G. Schütz laboratory in Heidelberg to develop molecular genetic tools to study gene function in mice by tissue-specific gene inactivation using the Cre/loxP system.

In 2001 he created the Unité CNRS UMR7148 (Molecular Genetics, Neurophysiology and Behaviour) at the Collège de France in Paris. There he focuses on the function of transcription factors that are induced by environmental cues, such as GR, AR and Stat5, developing and analysing mouse animal models with cell-specific deletions or over-expression of relevant genes. His work is devoted to the study of brain function analysing behaviours such as anxiety, despair, learning and memory and drug addiction

His group composed of 10 persons has recently incorporated the team of Jean-Pol Tassin that focuses on behavioural, neuropharmacological and electrophysiological approaches to drug addiction in rodents.

Dr. Célérier will be responsible of WP8 (Dissemination and exploitation plans) and will be in close touch with the co-ordinator and with the other two SMEs in order to fulfil her tasks.

Panlab has been working for more than 30 years at satisfying the needs of the housing for investigation animals, such as the supply of feed meals or cages and accessories, also projects, designs, develops and manufactures the products of the LETICA line, which cover the process from the first link in the instrumental chain to the software for the acquisition and processing of data. For this they have staff covering electronic, computer and mechanical engineers, biologists, veterinarians, all extensively qualified for the task undertaken. In this range Panlab, S.L. is the company that can guarantee to users the fullest support in the setting up of the experimental biological equipment. Its annual turnover has increased 8 % average each one of these last three years while profit has remained constant, meaning we are constantly renovating and evolving our business model in order to better accommodate to the flexible and changing nature of the market. The number of employees has moved from 28 to 35 in the same period and increased from 3 to 10 our work force in terms of RTD+I, clearly indicating they believe knowledge and constant reinterpretation of the market needs are to become their core business over the short term.

Dr. Célérier holds a PhD degree in Biology and has a very good experience in neuropharmacology, with a good record of publications in high quality scientific journals. This company will take care of the design, set-up and validation of all devices needed for the correct phenotypical characterisation of the animal models using classical behavioural approaches