Unraveling The Neural Circuitry Of Context-induced Relapse To Alcohol Seeking After Punishment-imposed Abstinence
Funder
National Health and Medical Research Council
Funding Amount
$528,016.00
Summary
Alcohol use disorder (alcoholism) causes significant social and economic costs to Australian society. Alcoholism is a brain disease, and relapse during abstinence is the main problem in successful treatment. In this project, we use an animal model of relapse to alcohol seeking after abstinence imposed by a negative consequence (punishment). This project will identify brain regions which can be targeted in future clinical studies in human alcoholics.
Ecstasy, Methamphetamine And Their Combination: Assessment Of Adverse Effects
Funder
National Health and Medical Research Council
Funding Amount
$384,250.00
Summary
MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour a ....MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour and memory impairment. However the link between MDMA and METH use and subsequent brain damage is still very controversial. Recently, we have found that when MDMA and METH are combined, a particularly toxic effect is seen with very high body temperatures and lasting adverse effects on mood and brain function. This is a major cause for concern because of evidence that many Australian drug users are combining METH and MDMA on a regular basis. This project will investigate the short and long-term effects of MDMA, METH and METH-MDMA combinations. Phase 1 is aimed at investigating whether different doses of the drugs lead to lasting changes in mood, behaviour and brain function and to compare the relative toxicity of the three treatments. Phase 2 will determine whether lack of fluid intake, high environmental temperatures and advanced age are risk factors in determining the toxicity of MDMA and METH. Phase 3 will assess whether the toxicity of these drug treatments depends upon whether an animal takes the drugs voluntarily or whether they are injected with the drug by the experimenter. The final part of the project will use a wide variety of advanced techniques to track the brain damage caused by these drug treatments given under a range of conditions. The significance of this project will be in increasing our understanding of how MDMA and METH affect the brain and behaviour and how the harms posed by these drugs may be predicted and therefore minimised.Read moreRead less
Investigation Of Novel Therapeutic Targets For The Treatment Of Drug Addiction
Funder
National Health and Medical Research Council
Funding Amount
$294,892.00
Summary
Drug abuse remains one of the world’s leading health care problems and the current drugs available to treat drug addiction are largely ineffective. This project aims to investigate the potential of a novel therapeutic target for the treatment of drug addiction with has the capacity for substantially reduced off-target effects.
This is an application for reappointment as a Principal Research Fellow. My primary area of research is preclinical studies of addiction, with a particular emphasis on relapse. I am increasingly engaged in translational studies.
Repurposing An Alzheimer’s Trial Drug To Block Relapse In Cocaine Addiction Models
Funder
National Health and Medical Research Council
Funding Amount
$1,050,601.00
Summary
Repeated exposure to drugs of abuse, such as cocaine, alters the reward circuitry of the brain. Enduring changes in the connections between neurons underlie addiction-related behavioural patterns, drug craving and the propensity for relapse after drug withdrawal. The pre-clinical research in this proposal aims to test whether blocking the function of a particular brain protein in mice can prevent relapse in two different paradigms that model cocaine addiction in humans.
The Orexin System: A Link Between Addiction And Depression
Funder
National Health and Medical Research Council
Funding Amount
$378,426.00
Summary
Relapse represents the most significant barrier to the successful treatment of addiction Interestingly, relapse rates are significantly higher amongst addicts with a concurrent mood disorder such as depression. This fellowship will use a number of cutting-edge techniques to explore the role of a hypothalamic peptide called 'orexin' in both relapse and depression and will thereby guide translational research aimed at developing pharmacotherapies designed to treat these disorders.
Structure-based Drug Design For Neuroprotection From Traditional Chinese Medicine
Funder
National Health and Medical Research Council
Funding Amount
$245,968.00
Summary
In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative di ....In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative disease.Read moreRead less
Development Of Pthaladyn-based Dynamin I-selective Inhibitors For Treatment Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$564,310.00
Summary
About 1% of the World�s population suffers from epilepsy; 30% fail to respond to anti-epileptic drugs (AED). Current AED development pathways have changed little in the past 20 years with the majority of current AEDs dampening the release of crucial chemical signals 24/7. Our new drugs, which inhibit a protein called dynamin, are only recruited at the onset of a seizure. Our approach will significantly enhance the day to day lives of those afflicted by epilepsy.
Inhibitory Neurotransmitter Receptors As Therapeutic Targets For Chronic Pain And Anxiety Disorders
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
There are currently few effective long-term treatments for chronic pain and anxiety disorders. Here we propose to develop innovative therapies for both of these debilitating neurological disorders. In addition, we plan to improve our current understanding of how these disorders occur in the first place. This may identify novel potential therapeutic strategies for treating pain, anxiety and a host of other neurological disorders.
Clinical Utility And Cost-effectiveness Of Genome Sequencing For Refractory Epilepsy In Children And Adults: A Multicentre Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$720,609.00
Summary
A large number of genomic variants have been found to underpin common types of epilepsy and to predict adverse drug reactions. However, the adoption of genomic testing in the routine management of epilepsy is hampered by uncertainties around its clinical utility and cost-effectiveness. This randomised controlled trial aims to determine the diagnostic efficiency, clinical and psychosocial impact, and cost-effectiveness of whole genome sequencing for refractory epilepsy in children and adults.