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Prof. Dr. Rainer Spanagel

The Institute of Psychopharmacology is primarily concerned with addiction research. The focus of our interest is the animal experimental and translational research of alcohol and drug addiction. Since addictive behavior often occurs with other psychiatric disorders, especially anxiety, depression, and ADHD, we also study these comorbidities. We also conduct research on social exclusion and borderline personality disorders.

Six research groups are affiliated to the Institute of Psychopharmacology: In Silico Psychopharmacology (Hamid R. Noori), Behavioral Genetics (Ainhoa Bilbao), Neuroanatomy (Anita C. Hansson), Molecular Psychopharmacology (Wolfgang H. Sommer), Translational Psychopharmacology (Marcus Meinhardt), Physiology of Neural Networks (Georg Köhr).

Based on preclinical findings, we pursue three objectives:

  • the development of new behavioral therapies, pharmacological interventions and neuromodulatory approaches in addicted patients (e.g. pharmacological suppression of drug memory reconsolidation)

  • to clarify the neurobiological long-term consequences of drug abuse and binge drinking in adolescents

  • the identification of risk factors for addictive disorders and development of preventive strategies

We use a wide range of methods to pursue our goals. In the field of behavioural pharmacology we use a variety of standard models (e.g. Reinstatement Model) and two new animal models for the generation of alcohol-addicted and cocaine-addicted rats respectively. These addiction models are the starting point for characterizing the neuroanatomical and molecular substrates of addictive behavior. Furthermore, these models are used to preclinically test new anti-relapse compounds in cooperation with the pharmaceutical industry.

For this purpose we additionally use in silico methods such as drug repurposing. Furthermore, we investigate gene x environment interactions that contribute to an increased risk of addiction. For this purpose we use different transgenic animal models in interaction with the drug and environmental factors such as stressors. In translational research we use combined animal and human MRI based methods (spectroscopy, fMRI, phMRI, and anatomical MRI approaches with 9.4T and 3T scanners, respectively) as well as converging genomic analyses - candidate genes from genome-wide association studies and differential gene expression analyses are defined and then functionally validated in transgenic rat models. Another important translational approach is our in silico human brain bank where we are integrating –omics derived information (also on a single cell level) for alcohol, opiate, cocaine, cannabis and nicotine use disorders.

National and international joint research projects

DFG: CRC/TRR 265 “Losing and Regaining Control over Drug Intake: From Trajectories To Mechanisms To Interventions”, Spokesperson, Duration: 2023 – 2027 (2nd funding phase)

  • Subproject A05 “Towards neurobehavioral profiles of resilient and drug addicted rats”

BMBF: AhEAD – “Preclinical confirmatory study on the use of exosomes in the treatment of alcohol addiction”, project coordination, Duration: 2020 – 2023

BMBF: ERA-Net NEURON 2019 – 2022: Psi-Alc - Preclinical Phase II Testing of Psilocybin in Alcohol Addiction”, Duration: 2019 – 2023

DFG: CRC/TRR 265 “Losing and Regaining Control over Drug Intake: From Trajectories To Mechanisms To Interventions”, Duration: 2019 – 2023 (1st funding phase)

  • Subproject “Intensive behavioral monitoring and dynamical state transitions in animal models of addiction”

BMBF: A systems-medicine approach towards distinct and shared resilience and pathological mechanisms of substance use disorders (SysMedSUDs). Coordinator, Duration: 2019 – 2023

BMBF: Target-OXY 031L0190A “Towards a targeted treatment of alcohol addiction with oxytocin”, Duration: 2019 – 2023

DFG: Heidelberg Pain Consortium SFB 1158: “From nociception to chronic pain: Structure- function properties of neural pathways and their reorganization” / 2nd funding period, Duration: 2019 – 2023

  • Subproject B04 “Towards a mechanism-specific intervention of thalamo-limbic pain processing”

DFG: RTG 2350 “Impact of Adverse Childhood Experiences on Psychosocial and Somatic Conditions Across the Lifespan”, Duration: 2018 – 2024

  • Subproject “The Impact of Early Social Adversity on Social and Emotional Competence in Later Life and the Underlying Neurobiological Mechanisms”
  • Subproject “The Impact of Early Social Adversity on the Development of Myofascial Low Back Pain – an Animal Experimental Study”

Legend: DFG = German Research Foundation, BMBF = Federal Ministry of Education and Research,  CRC/TRR = transregional Collaborative Research Center, RTG = Research Training Group

Selected publications

  1. Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications.
    Bilbao A, Spanagel R. BMC Med. 2022. 20(1):259.
  2. The inhibition of RasGRF2, but not RasGRF1, alters cocaine reward in mice. Bernardi RE, Olevska A, Morella I, Fasano S, Santos E, Brambilla R, Spanagel R. J Neurosci. 2019.  39(32):6325-6338
  3. Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs.
    Noori HR, Mervin LH, Bokharaie V, Durmus Ö, Egenrieder L, Fritze S, Reinhardt G, Schabel HH, Staudenmaier S, Logothetis NK, Bender A, Spanagel R. Nat Commun. 2018. 9(1):4699
  4. Dnmt3a2 in the nucleus accumbens shell is required for reinstatement of cocaine-seeking.
    Cannella N, Oliveira AMM, Hemstedt TJ, Lissek T, Bading H, Spanagel R.  J Neurosci. 2018. 38(34):7516-7528
  5. A multiscale cerebral neurochemical connectome of the rat brain.
    Noori HR, Schöttler J, Ercsey-Ravasz M, Cosa-Linan A, Varga M, Toroczkai Z, Spanagel R. PLoS Biol. 2017. 15(7):e2002612
  6. Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence.
    Hirth N, Meinhardt MW, Noori HR, Salgado H, Torres-Ramirez O, Broccoli L, Vengeliene V, Roßmanith M, Perreau-Lenz S, Köhr G, Sommer WH, Spanagel R, Hansson AC. Proc Natl Acad Sci U S A. 2016. 113(11):3024-9
  7. Enhanced functional activity of the cannabinoid type-1 receptor mediates adolescent behavior.
    Schneider M, Kasanetz F, Monory K, Leweke FM, Schreckenberger M, Lutz B, Reggio PH, Manzoni OJ, Spanagel R. J Neurosci. 2015. 35(41):13975-88
  8. Glutamate receptors on dopamine neurons control the persistence of cocaine seeking.
    Engblom D, Bilbao A, Sanchis-Segura C, Dahan L, Perreau-Lenz S, Balland B, Parkitna JR, Luján R, Halbout B, Mameli M, Parlato R, Sprengel R, Lüscher C, Schütz G, Spanagel R (2008) Neuron 59(3):497-508.
  9. The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption.
    Spanagel R, Pendyala G, Abarca C, Zghoul T, Sanchis-Segura C, Magnone MC, Lascorz J, Depner M, Holzberg D, Soyka M, Schreiber S, Matsuda F, Lathrop M, Schumann G, Albrecht U. Nat Med. 2005. 11(1):35-42.
  10. Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Sillaber I, Rammes G, Zimmermann S, Mahal B, Zieglgänsberger W, Wurst W, Holsboer F, Spanagel R. Science. 2002. 296(5569):931-3.

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Contact

Central Institute of Mental Health
J 5
68159 Mannheim

Phone +49 621 1703-6251
Fax +49 621 1703-6255

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