Cocaine Addiction and α2-GABAA Receptors

The laboratory is part of an MRC-funded multidisciplinary “addiction cluster”. Understanding the basic neurobiological mechanisms by which drugs of abuse become addictive is essential for the future development of strategies to combat drug addiction. Addictive drugs have in common that they influence the function of the pathways in the brain mediating reward, particularly the nucleus accumbens, a region which consists almost exclusively GABA-ergic neurones. Our collaborators studying cocaine addicts have implicated the α2-GABAA receptor isoform in cocaine abuse. In agreement, we reported that these receptors are expressed in the nucleus accumbens and importantly that certain behavioural effects of cocaine are prevented by deletion of the α2 subunit gene. You will be trained to utilize electrophysiological, behavioural and molecular biology techniques to elucidate the physiological role of α2-GABAA receptors in the reward circuitry and the key role these receptors play in cocaine addiction. Such research should allow a better understanding of how genetics can cause vulnerability to drug abuse and influence the design of new pharmacological approaches to treat addictions.

References

Dixon, C. I., Belelli, D., Lambert JJ. et al., (2010). Cocaine effects on mouse incentive-learning & human addiction are linked to α2-subunit containing GABAA receptors. Proc.Natl. Acad. Sci. USA. 107: 2289-2294.

Anstee, Q., Belelli, D., Lambert, J.J., et al., (2013). Mutations of the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. Nature Commun. 4: 2816 doi:10.1038/ncomms3816

Maguire, E.P., Macpherson, T., Swinny, J., Dixon, C.I., Herd, M.B., Belelli, D., Stephens, D.N., King, S.L., Lambert, J.J. (2014). Tonic inhibition of accumbal spiny neurons by extrasynaptic α4bδ GABAA receptors modulates the actions of psychostimulants. J. Neurosci., (In press).

Supervisor: 
Professor Jerry Lambert
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