Addiction Neuroscience Group
Alcohol and smoking both contribute to a significant number of hospitalisations and deaths daily. Many of these deaths are preventable and demonstrate the urgent need for improved therapeutic strategies. In our group, we study how alcohol and other drugs change the brain’s chemistry, structure and function. Our research into the motivation to seek and consume alcohol has identified circuits, neurotransmitters, and novel drug targets. We continue to unravel the circuitry and brain chemistry involved in alcohol-seeking. With our innovative program of research, we directly address alcohol-related problems using robust animal models, best-practice research pipelines, key strategic collaborations, clinical and pharma partners.
- The impact of alcohol on the brain
- Neural circuitry of alcohol-seeking behaviours
- Identifying novel therapeutic targets
- Interactions between stress and alcohol use
- Sex differences in binge drinking
- Alcohol and metabolic hormones
- Addiction-like behaviours in obesity
- Behavioural models
- Fiber photometry
- Viral tracing
About our research
In Australia alone, alcohol hospitalises >400/day and kills >15 people/day (Turning Point), while smoking causes ~55 deaths/day. These deaths are largely preventable and demonstrate the urgent need for improved therapeutic strategies. While behavioural intervention will be part of the remedy, these afflictions are quintessentially neurochemical in their origins and, if properly understood, should respond to appropriate neuropharmacological interventions. Our innovative program of research directly addresses these problems with robust animal models, best-practice research pipelines, key strategic collaborations, clinical and pharma partners.
In our group we study how alcohol and other drugs change the brain’s chemistry, structure and function. Our research into the motivation to seek and consume alcohol has identified circuits, neurotransmitters and novel drug targets with significant knowledge gain around mechanisms that underpin relapse, a major issue for treatment success. For example, we were the first to demonstrate that the orexin system was critically involved in relapse to alcohol-seeking. Over the last 15 years we have shown that orexin is a pivotal driver of alcohol-seeking, even after prolonged abstinence and identified brain nuclei where this effect is mediated. Further, we designed the world’s first double-blind placebo-controlled trial of Belsomra® (suvorexant; a drug that targets the orexin system; NCT03897062) for treating AUD.
We continue to unravel the circuitry and brain chemistry involved in alcohol-seeking. Using a validated back-translation approach we identified muscarinic M4 receptors as a novel therapeutic target for alcohol use disorder. More recently, we have identified an ion channel that appears to play key roles in both controlling intake and the somatic signs of withdrawal following dependence. We are actively pursuing these lines of enquiry, along with other projects listed below and research in collaboration with the Fluid Homeostasis Group.
‘Our research vision is to contribute to improved treatment options for alcohol use disorder (AUD). We elucidate neural and chemical mechanisms driving the motivation to obtain and consume alcohol and thereby identify and validate novel potential therapeutic targets that can be empirically tested in robust animal models and ultimately in human subjects.’
- Annai Charlton
- Anna Horton
- Xavier Maddern
- Kade Huckstep
- Sean Murphy
- Shivani Vaidya
- Eva Guerrero-Hreins
- Walker, L.C., Berizzi, A.E., Chen, N.A., Rueda, P., Perreau, V.M., Huckstep, K., Srisontiyakul, J., Govitrapong, P., Xiaojian, J., Lindsley, C.W., Jones, C.K., Riddy, D.M., Christopoulos, A., Langmead, C.J. and Lawrence, A.J. (2020). Acetylcholine muscarinic M4 receptors as a therapeutic target for alcohol use disorder: Converging evidence from humans and rodents. Biological Psychiatry. doi:https://doi.org/10.1016/j.biopsych.2020.02.019.
- Walker, L.C., Huckstep, K.L., Chen, N.A., Hand, L.J., Lindsley, C.W., Langmead, C.J. and Lawrence, A.J. (2021). Muscarinic M 4 and M 5 receptors in the ventral subiculum differentially modulate alcohol seeking versus consumption in male alcohol‐preferring rats. British Journal of Pharmacology, 178(18), pp.3730–3746. doi:https://doi.org/10.1111/bph.15513.
- Maddern, X.J., Walker, L.C., Campbell, E.J., Arunogiri, S., Haber, P.S., Morley, K., Manning, V., Millan, E.Z., McNally, G.P., Lubman, D.I. and Lawrence, A.J. (2022). Can we enhance the clinical efficacy of cognitive and psychological approaches to treat substance use disorders through understanding their neurobiological mechanisms? Neuroscience & Biobehavioral Reviews, 142, p.104899. doi:https://doi.org/10.1016/j.neubiorev.2022.104899.
- Murphy, S.C., Luca Godenzini, Robertas Guzulaitis, Lawrence, A.J. and Palmer, L.M. (2023). Cocaine regulates sensory filtering in cortical pyramidal neurons. Cell Reports, 42(2), pp.112122–112122. doi:https://doi.org/10.1016/j.celrep.2023.112122.