Institute for Psychopharmacology
Phone: +49 621 1703-6251
Fax: +49 621 1703-6255
Secretariat: Christine Roggenkamp, M.A.
Phone: +49 (0) 621 1703-6252, e-mail
Laboratory Building, 4th Floor, Room 402
The Institute focuses on animal-experimental addiction research and has implemented step-wise several translational components reflected especially by the MWK-funded WG Translational Addiction Research. Since addictive behavior is often associated with anxiety and affective disorders in the origin and over the lifetime course, these comorbidities are also taken into account. Our translational work is done in close collaboration with the Departments Addiction Medicine and Psychosomatics and Genetic Epidemiology in Psychiatry.
In the last five years we had a strong increase in third-party funding (BMBF, DFG, EU, MWK and industry) and research output. Of significance are the NGFN+ funded consortium on “Genetics of Alcoholism” (coordinator Spanagel) and the ERA-Net Neuron project on “Translational Neuroimaging in Alcoholism” (coordinator Sommer). The DFG provided the Reinhart-Koselleck-Award of 1.5Mill € to Spanagel for integrating a new technology -“optoMRI” – which allows a functional MRI approach in the animal scanner. As a result of these excellent quantitative measures we transformed into an institute in 2011 with six WGs providing a broad array of cutting-edge technologies and disciplines ranging from neuroanatomy, neurophysiology, multimodal neuroimaging to molecular and behavioural pharmacology and genetics. Miriam Schneider as a member of our institute got awarded with the first CIMH granted junior research group and continues on her outstanding research on cannabinoids and their role in the development of neuropsychiatric disorders. We also integrated in recent years in in-silico approaches (through funds of the Bernstein Center and NGFN+) under the leadership of Hamid R. Noori and have developed unique large scale modeling approaches in addiction and depression research.
Our research activities of the Institute perfectly align to the three research pillars of the CIMH structure and development plan and have delivered some key publications in these areas of research:
(1.) Mental disorders across the life span: We have studied alcohol use and the development of alcohol use disorders across life span in animal models and are now in a position to make some important conclusions about disease progression and severity and diagnostic markers for the human situation in a gender-specific manner which can be validated in longitudinal studies such as IMAGEN. For better matching with IMAGEN we have started to do longitudinal multimodal animal imaging studies. A master example of such a translational longitudinal neuroimaging approach has recently been provided by us showing by means of glutamate spectroscopy that glutamate levels during withdrawal are enhanced in alcohol dependent animals as well as in the brain of alcohol dependent patients. This is not only a key finding for the glutamate theory of addiction but provides also an avenue into spectroscopy-based diagnosis and treatment prediction as patients with high brain glutamate levels respond better to acamprosate. Most importantly, we have started to look into the long-term consequences of alcohol binging and / or cannabinoid use during adolescence and have discovered life-long alterations in cognitive, emotional and motivational processing.
(2.) Neuronal Plasticity: Through massive gene expression profiling and pathway analyses along with cell-type specific neuroanatomic mapping we have defined neurochemical and neuroanatomical substrates critically involved in several aspects of compulsive drug use and behaviour. Those findings are usually functionally validation by us by means of reverse genetic approaches with either inducible transgenic animals or targeted virus-mediated gene transfer. For example, we have defined infralimbic-accumbal projection neurons operating with glutamate as being critical for alcohol and cocaine-seeking behaviour. In these projection neurons metabotropic glutamate receptors (mGluR2) are strongly down-regulated in the addicted brain of a rat resulting in a glutamate-driven hyperexcitability – a finding that matches completely to the human situation as revealed by post-mortem brain studies in alcohol dependent patients.
(3.) Therapy research: We have developed DSM-IV/V-based animal models for alcohol and cocaine addiction that allow us to test new medications. Especially, our DSM-IV/V-like model for alcohol addiction is internationally well-recognized and has become the gold standard model in the pharmaceutical industry for testing new putative anti-relapse drugs. In fact, in collaboration or contract work, more than 50 compounds from 9 different companies have been tested with this model and 4 compounds have been put forward for clinical phase II testing; two of these – acamprosate and nalmefene - have been approved for clinical use (nalmefene has obtained approval by the European Medicines Agency in December 2012), demonstrating the high predictive power of this animal model. Within the framework of SFB636 we have developed new extinction and reconsolidation-based treatment approached waiting for the translation into the human condition. In collaboration with the Psychosomatic Clinic we have developed a new animal model on social exclusion in the context of KFO256 which will put us for the first time into a position to develop on a preclinical level new medications for borderline personality. Finally, we have developed unique in in silico-tools, that allow us to make treatment predictions without experimental efforts and to push drug repurposing to a novel level.
Zentralinstitut für Seelische Gesundheit (ZI) - https://www.zi-mannheim.de