Professor Sarah King
Inhibitory circuits influencing addiction
The predominant cell populations of the nucleus accumbens, a brain area implicated in addiction, are GABAergic. We are using genetic tools to manipulate expression of GABAA receptors in specific cell populations of the nucleus accumbens to:
- determine the role of GABAA receptors in addiction-related behaviours
- explore how chronic administration of drugs of abuse interacts with GABAergic signaling in the nucleus accumbens to influence behavior
- attempt to restore normal function in mice chronically treated with drugs of abuse.
A PhD project in my laboratory would contribute to answering these questions through the development and use of genetic tools. This might involve breeding and characterizing mice with gene manipulations of specific GABAA receptor subtype, or developing new viral strategies to up or down-regulate receptors. The project will have both molecular and behavioural components and would suit a student with a strong molecular biology and/or biological psychology background.
Key references
- Dixon CI., Walker SE., King SL. & Stephens DN. (2012) Deletion of the gabra2 Gene Results in Hypersensitivity to the Acute Effects of Ethanol But Does Not Alter Ethanol Self Administration, Plos One 7(10):e47135. doi: 10.1371/journal.pone.0047135.
- Peña-Oliver Y., Buchman VL., Dalley JW., Robbins TW., Schumann G., Ripley TL., King SL., Stephens DN. (2012) Deletion of alpha-synuclein decreases impulsivity in mice. Genes Brain Behav 11: 137-146. doi:10.1111/j.1601-183X.2011.00758.x PMID: 22142176
- Heath CJ.*, King SL.*, Gotti C., Marks MJ. & Picciotto MR. (2010) Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development via alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 35: 2324-38 (*co-first authors) doi:10.1038/npp.2010.130 PMID: 20736992
- Dixon CI., Morris HV., Breen G., Desrivieres S., Jugurnauth S., Steiner RC., Vallada R., Guindalini C., Lavanjeira R., Messas G., Rosahal TW., Atack JR., Peden DR., Belelli D., Lambert JJ., King SL., Schumann G. & Stephens DN. (2010). Cocaine effects on mouse incentive-learning and human addiction are linked to alpha2 subunit–containing GABAA receptors. Proc Natl Acad Sci U S A. 107(5):2289-94. doi: 10.1073/pnas.0910117107 PMID: 20133874.
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