Prof Andrew Lawrence (Florey)Title: Muscarinic Acetylcholine Receptors as a Novel Treatment Target for Alcohol Use Disorder
Abstract: Despite the large socioeconomic burden of alcohol use disorders (AUD), therapeutic treatment options are limited. There is a need to characterise the underlying neurochemistry driving alcohol seeking to identify and evaluate novel treatment targets. To this end we conducted genome-wide RNA sequencing in the striatum from humans with AUD and healthy controls and concurrently examined receptor expression in the corresponding brain regions in rat following chronic alcohol consumption/withdrawal. In the brains from humans with AUD we found reduced expression of muscarinic M4 receptors, which was limited to the putamen. In line with this, expression of the same receptor was decreased in the rat dorsolateral striatum (plus other regions). These findings have been extended to mouse striatum by a collaborating laboratory. Further, administration of an M4 Positive Allosteric Modulator to target M4 receptors reduced alcohol self-administration and relapse, without effects on natural reward consumption or sedation. Collectively, our data identify a novel treatment target for AUD. We are in the process of trying to translate this finding.
Bio:
Professor Andrew Lawrence is a Senior Principal Research Fellow & Deputy Director at the Florey Institute of Neuroscience & Mental Health where he runs the Addiction Neuroscience laboratory. Andrew has published over 300 original articles & reviews, with >14,800 citations (H index 64). Andrew was Treasurer of the Australian Neuroscience Society (2002-2008), President of the Asian-Pacific Society for Neurochemistry (2014-16) & is currently President-elect of the International Society for Biomedical Research on Alcoholism. He is Editor-in-Chief of the Journal of Neurochemistry and an Honorary Fellow of the British Pharmacological Society for “sustained excellence and leadership in pharmacology”. To date Andrew has delivered 11 plenary lectures such as the 2017 Lawrie Austin lecture at Australasian Neuroscience Society and the 2021 Plenary at the Japanese Society for Neurochemistry. He was recently invited to speak at the 2024 Gordon Research Conference on Alcohol and the Nervous System. Andrew’s research leadership extends to being a passionate mentor, many of his students/postdocs are now in successful academic appointments around the world. He embraces diversity and inclusion and has striven to create a safe and supportive environment where people can flourish. As a behavioural neuropharmacologist, Andrew studies basic mechanisms relevant to addiction and motivated behaviour patterns. He is recognised for developing rodent models to understand the neurochemical basis of drug-seeking and drug-induced adaptations. His lab’s focus is to identify and validate new therapeutic targets for drug and alcohol abuse.