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Drug addiction is a major health and medical problem in Australia. It is a chronically relapsing condition for which there are few effective treatments. This project identifies novel circuits within the brain which are responsible for inhibiting drug taking. It will provide new knowledge on how we may able to prevent relapse to drug taking and so promote and maintain long -term abstinence.
AKR1C3 As A Potential Biomarker For Sensitivity Of T-lineage Acute Lymphoblastic Leukaemia To The Pre-prodrug PR-104
Funder
National Health and Medical Research Council
Funding Amount
$327,797.00
Summary
Multiagent chemotherapy is the most effective modality for the treatment of childhood ALL, the most common paediatric malignancy. Despite dramatic improvements in survival over the past 40 years, relapsed ALL remains one of the most common causes of death from disease in children. Therefore, innovative strategies are needed to benefit those children who respond poorly to established therapy. This application will test a novel therapy for a very aggressive subtype of childhood leukaemia.
Brain Circuits Promoting Abstinence And Preventing Relapse To Alcohol Seeking
Funder
National Health and Medical Research Council
Funding Amount
$591,995.00
Summary
This project maps and manipulates the brain circuits that promote abstinence from alcohol use. It uses new techniques from neuroscience to control the activity of specific cell types in discrete brain circuits. In this way we can alter the activity of these circuits to build on the normal neural restorative processes that occur during abstinence from alcohol use to reduce, and possibly prevent, relapse.
The brain plays a major role in the overconsumption of high fat/high sugar foods and this contributes to obesity but it receives little attention when it comes to developing novel treatments. My lab showed that a FDA-approved smoking cessation medication, that is a nicotinic receptor modulator, decreased the overconsumption of sugar. This project aims are to identify which nicotinic receptors and brain circuits are involved in the overconsumption of sucrose to improve treatments for obesity.
Fear Relapse: Neural Substrates Underlying Its Inhibition And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$437,476.00
Summary
Exposure-based therapies are effective for anxiety disorders such as post traumatic stress, but two challenges remain: 1) patients that have learned to inhibit their fear are likely to relapse, requiring further therapy; 2) many drop out of therapy since it is aversive and anxiety provoking. We use an animal model to: 1) identify the neural substrates underlying fear inhibition; and 2) determine the conditions that prevent relapse and encourage participation in treatment.
A Memory Retrieval - Extinction Procedure To Prevent Relapse To Drug Seeking
Funder
National Health and Medical Research Council
Funding Amount
$387,929.00
Summary
This project shows how relapse to drug seeking can be modulated, and possibly prevented, by novel approaches that manipulate the stability of drug related memories.
A New Therapeutic Target For Stress-related Relapse
Funder
National Health and Medical Research Council
Funding Amount
$685,266.00
Summary
Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. We have identified a novel system in the brain for the regulation of stress-induced relapse. Successful completion of this project will indicate improved pharmacotherapeutic strategies for the treatment of alcoholism and drug abuse. Given the scale and costs of substance abuse disorders, improved therapeutic approaches will have immediate and sustained impact.
Mapping And Manipulating Circuits For Relapse And Abstinence
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
Alcohol-use disorders and other drug addictions are chronically relapsing conditions. Current treatment approaches have only modest efficacy. Two advances are needed for genuine improvement. The first is parsing the brain mechanisms supporting abstinence and relapse at cellular as well as circuit levels. The second is targeting these circuits therapeutically with the same precision. This project contributes to the first advance and lays a basic science platform for next generation therapeutics.
Microenvironmentally Induced Acute Lymphoblastic Leukemia Cell Quiescence And Chemotherapy Evasion
Funder
National Health and Medical Research Council
Funding Amount
$672,885.00
Summary
Although almost all patients with ALL achieve a remission, a proportion of children and the majority of adults relapse following treatment. Relapse occurs as a result of a small number of malignant cells that survive chemotherapy. We have identified a population of quiescent cells that could represent this population. We believe this population is defined by its location in the bone marrow. This project will characterize this population and determine whether it is protected from chemotherapy.
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.