Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gaining control over drug-seeking behavior in alcohol dependence

29.05.2013
The damaging effects of too much alcohol on the brain are widely known, but often neglected, and poorly understood.

New data provided by the working group “Molecular Psychopharmacology” at the Institute of Psychopharmacology at the Central Institute of Mental Health (ZI) offers a fundamentally new insight into the molecular basis by which repeated alcohol intoxication causes a substantial and long-lasting reorganization of the medial prefrontal cortex, a structure that participates in higher order brain functions, commonly referred to as executive functions.

The working group “Molecular Psychopharmacology”, led by Wolfgang H. Sommer, investigates genetic, neurobiological and behavioral factors contributing to addictive behaviors. In this context the group focuses on long-term consequences of alcohol in the brain, in particular how these affect the prefrontal cortex (PFC). A new paper, published in February by the Journal of Neuroscience, shows that alcohol damages a small sub-region of the PFC called the infralimbic area, but that rats can regain control over pathological alcohol seeking behavior after repairing this functional deficit.

Specifically, the researchers show that a subgroup of PFC neurons is particularly sensitive to the long-term consequences of repeated alcohol intoxications (blood alcohol concentrations > 2.5 g/l, a level that is typically observed in alcoholic patients). These neurons become unable to adequately control the release of their signaling substance glutamate due to a lack of autoreceptor function normally provided by glutamate receptors of the mGluR2 type. Sommer’s team can directly link this loss of function to escalated alcohol seeking because restoring mGluR2 levels in infralimbic projection neurons by focal virus-mediated gene transfer was sufficient to abolish the excessive seeking response completely. The translational value of the findings from experimental animals is supported by data from human postmortem brains showing a reduction in mGluR2 expression in a corresponding PFC region of alcoholics.

These results suggest that mGluR2 loss in rodent and human neural circuits, which provide cortical control over deeper brain structures involved in motivational and emotional regulation, may be a major consequence of alcohol dependence and a key pathophysiological mechanism for the increased propensity to relapse. Given that it seems possible to restore PFC control over drug seeking behavior by repairing mGluR2 autoreceptor function, it now becomes important to understand the molecular mechanism leading to the blockade of receptor expression. Assuming that epigenetic silencing plays role in this process, the working group “Molecular Psychopharmacology” is now aiming to design interventions for removing such epigenetic marks.
Contact:
PD Dr. Wolfgang H Sommer
Group Leader of the Working Group Molecular Psychopharmacology
Institute for Psychopharmacology, Central Institute of Mental Health
phone ++49 (0)621 1703-6286
E-Mail: wolfgang.sommer@zi-mannheim.de

Publication:
Meinhardt MW, Hansson AC, Perreau-Lenz S, Bauder-Wenz C, Stählin O, Heilig M, Harper C, Drescher KU, Spanagel R, Sommer WH. Rescue of infralimbic mGluR2 deficit restores control over drug-seeking behavior in alcohol dependence. J Neurosci. 2013 Feb 13;33(7):2794-806.

doi: 10.1523/JNEUROSCI.4062-12.2013. PMID: 23407939.

Sigrid Wolff | idw
Further information:
http://www.zi-mannheim.de

More articles from Health and Medicine:

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>