Orexins and Appetitive Motivation

Preclinical evaluation of the orexin system.


Honours student at the Florey Institute of Neuroscience and Mental Health (2011-2012).

PhD student at the School of Psychology, UNSW Sydney (2013-2017).

The Orexins

The orexins are a neuropeptide system originating the hypothalamus and projecting widely throughout the brain. The two ligands bind with varying affinity for two G-protein coupled receptors.

Honours: Orexin-2 receptors and alcohol-seeking

My honours project involved studying the orexin system using targeted microinjections of an OX2 receptor antagonist prior to alcohol self-administration and reinstatement. I showed that central administration of OX2 antagonist reduced self-administration but not reinstatement and that this effect was due to the role of OX2 receptors in the nucleus accumbens core, but not the shell. I also worked with other lab members on projects targeting the OX1 receptor in the prelimbic cortex and ventral tegmental area. My involvement in both of these projects resulted in 2 co-first author empirical papers and a first author review paper. These papers are important for the field, particularly because the OX2 receptor has been understudied relative to the OX1 receptor, and together they have accumulated close to 100 citations.

Doctorate: Potential clinical utility of dual orexin receptor antagonists

During my PhD, I continued to utilise targeted microinjection techniques to study appetitive motivation for alcohol, nicotine and palatable food. The aim of my project was to evaluate whether a dual orexin receptor antagonist, from the same drug-class as the clinically approved suvorexant, was a potential therapeutic for addiction. I studied the effect of dual orexin antagonism in self-administration and reinstatement for these reinforcers at a variety of doses, schedules of reinforcement and different motivational states. My work on the orexin system resulted in two first-author empirical papers, that have called for a more cautious approach to using orexin therapeutics in addiction. My paper on the orexin system and nicotine was ranked in the top 16 for the ECNP Preclinical Network Data Prize. I also published a first-author empirical paper optimising aspects of animal welfare, a first-author review paper describing the role of contexts in drug-seeking, a journal club paper discussing reinstatement of drug-seeking and a book chapter on the orexins and nicotine.