As part of their Addiction Research Strategy the MRC have established 11 Research Clusters of experts from different disciplines and different institutions who, when brought together in a critical mass, will be able to make an impact in this area.
One of the Clusters is organised around investigations into the role of the brain’s major inhibitory transmitter, GABA in addiction processes.
The objective of the GABA project is to understand how GABAergic systems operate in neuronal circuits underlying reward, and motivation on the one hand and in circuits that allow the brain to control and veto spontaneous reactions to obtain alcohol and drugs. If we can understand these processes, we may be able to design treatments for when they go wrong.
The cluster brings together scientists working at many levels to understand these complex processes.
We study:
- How manipulations of subtypes of receptors for GABA operate in brain areas known to be important for reward, change communication between nerve cells and alter reward processes
- How manipulations of receptor subtypes lead to increased propensity to drink alcohol
- How stress works on these systems to increase drug and alcohol abuse
- How subtle variations in genes for GABA receptors influence human behaviour in response to stress and to drug cues. Such knowledge will help identify individuals at risk of addiction as a result of subtle differences in the function of their GABAA receptors.
- Which brain areas are influenced by drugs, stress and drug cues, and how treatments based on GABAergic drugs may improve brain function to overcome addictive behaviour.
The GABA Cluster includes: clinicians involved in treating addicted patients, key experts in brain imaging, in molecular genetics, electrophysiology, psychology and behavioural analysis, as well as colleagues from industry who will be able to take our findings into programmes for developing new treatments.
See also
Publications from the GABA Cluster
Dixon CI, Walker SE, King SL and Stephens DN. Deletion of the gabra2 gene encoding GABAA a2-subunits results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration PLoS One 7:e47135 (2012)
Panzanelli P, Gunn BG, Schlatter MC, Benke D, Tyagarajan SK, Scheiffele P, Belelli D, Lambert JJ, Rudolph U, Fritschy JM. Distinct mechanisms regulate GABAA receptor and gephyrin clustering at perisomatic and axo-axonic synapses on CA1 pyramidal cells. J Physiol. 2011 Oct 15;589 (Pt 20):4959-80.
Dixon CI, Morris HV, Breen G, Desrivieres S, Vallada H, Rosahl TW, Belelli D, Lambert J, Guindalini C, Laranjeira R, Messas G, King SL, Atack JR, Schumann G and Stephens DN. Cocaine effects on mouse incentive-learning and human addiction are linked to a2-containing GABAA receptors. Proc Natl Acad Sci USA 107: 2289-2294 (2010)