Nicotine abuse is the single greatest preventable risk factor for physical illness and death in Australians. Our understanding of the neural and cognitive mechanisms that underlie the transition from use to dependence is yet to be understood. The current proposal investigates the neural mechanisms underlying cognitive control, critical to self-control over the impulse for drug rewards, in non-dependent and dependent nicotine users.
A Novel Knockin Model To Test The Role Of Nicotine Acting On Alpha4 Acetylcholine Receptors In Complex Behaviours
Funder
National Health and Medical Research Council
Funding Amount
$581,315.00
Summary
Cigarette smoking is the single largest preventable cause of death and disease in Australia and worldwide. Nicotine contained in tobacco products acts on brain nicotine receptors, which plays an intrinsic role in addiction. One type of receptor for nicotine found in regions of the brain associated with drug-seeking behaviour is called alpha4 nicotinic receptors. We have made a mouse with a mutation in this nicotine receptor to study nicotine addiction and anxiety.
Targeting Alpha-conotoxin MII To Inhibit Neuronal Nicotinic Acetylcholine Alpha3beta2 Receptors Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$218,334.00
Summary
Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique ....Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique tools with which to identify and determine the physiological role, played by the different native neuronal nAChRs. Moreover, they are unusually stable peptides and can withstand enzyme and acid treatment. These findings have encouraged us to pursue the viability of alpha-conotoxin MII as a new and selective antagonist for the neuronal nictotinic receptor alpha3 beta2 which is involved in nicotine addiction. The challenge and major goal of this project is to deliver alpha-conotoxin MII efficiently into the brain. A-Prof Toth has developed a novel drug-delivery system for the oral administration of drugs and peptides, which in their unmodified form are poorly absorbed or biologically unstable. In this project alpha-conotoxin MII will be combined with a specifically designed lipopolysaccharide delivery system . The delivery system can be specifically tailored to transport a wide variety of peptides through the different biological barriers. The peptides can be conjugated to the delivery system in such a way as to release the peptide after it has been absorbed (prodrug), or to form a biologically stable and active novel molecule. The outcomes of this work will include the first delivery system of nicotinic antagonists to the brain and new knowledge concerning the importance of the neuronal nictotinic receptor alpha3 beta2 in nicotine addiction.Read moreRead less
Efficacy Of Education And Advice Delivered By Text Message To Aid Smoking Cessation
Funder
National Health and Medical Research Council
Funding Amount
$538,395.00
Summary
A high proportion of smokers indicate a desire to stop smoking and report having made attempts to quit. However, most attempts are not successful and new methods are needed to support motivated smokers and improve success rates. This project evaluates the use of text messages to deliver advice and support to smokers motivated to stop smoking. We aim to understand if and how this promosing new intervention helps smokers to quit.
Cognitive Phenotyping And Personalised Treatment For Methamphetamine Addiction
Funder
National Health and Medical Research Council
Funding Amount
$483,402.00
Summary
Prevention and treatment of addiction to stimulants such as methamphetamine is imperative for community health and safety. This fellowship will enable me to apply my expertise in impulsivity and addiction to identify people at risk of increasing methamphetamine use and to develop and evaluate cognitive training therapies that will empower people with methamphetamine related problems to control their drug use. Outcomes include a risk identification and triage tool and three novel therapies.
An Open-label Randomised Pragmatic Policy Trial Of Nicotine Products For Short-term Cessation Assistance Or Long-term Substitution In Smokers.
Funder
National Health and Medical Research Council
Funding Amount
$1,053,910.00
Summary
Many smokers who try to quit fail in their attempt. Medicinal nicotine is currently only used as a short-term quit aid. This trial will test if offering smokers the option of using these products as long-term substitutes for cigarettes will help more smokers to successfully quit. We will also determine if offering smokers low toxicity smokeless tobacco and electronic nicotine devices in addition to medicinal nicotine products further increases the number of smokers who quit successfully.
Contextual Control Over Relapse To Drug Seeking: Behavioural And Neural Mechanisms.
Funder
National Health and Medical Research Council
Funding Amount
$395,750.00
Summary
Drug addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. Prolonged drug use is associated with increased rates of physical problems (e.g., cardiovascular disease), mental health problems (e.g., depression and anxiety), and criminal involvement (e.g., property crimes and incarceration). A defining feature of drug addiction is that it is a chronically relapsing condition. Between ....Drug addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. Prolonged drug use is associated with increased rates of physical problems (e.g., cardiovascular disease), mental health problems (e.g., depression and anxiety), and criminal involvement (e.g., property crimes and incarceration). A defining feature of drug addiction is that it is a chronically relapsing condition. Between 60-80% of addicts attempting to give up drug taking will relapse to drug taking. The behavioural and brain mechanisms which underpin this persistent propensity to relapse are largely unknown. This project studies the behavioural and brain mechanisms for relapse to drug addiction. This project uses a well validated animal model of drug taking to ask why relapse occurs. It will identify some of the environmental antecedents to relapse and the brain mechanisms which mediate relapse. As such, this project will project will provide important information about relapse to drug addiction and may help identify targets for therapeutic intervention and possibly disrupt the addictive cycle.Read moreRead less
Drug addiction is a major health and societal problem in Australia. Relapse is among the most fundamental problems for addicts. This project studies the behavioural and brain mechanisms for relapse to drug seeking. It studies why relapse is more likely in some places than others; the brain mechanisms for this contextual control over relapse; and how relapse to seeking drug rewards is similar to and different from relapse to seeking non-drug rewards.
I am a psychologist who leads an internationally recognised program of research which aims to increase our understanding of alcohol and drug problems, prevent them where possible and improve treatment responses.
Understanding The Methamphetamine Epidemic And Its Implications For Service Provision And Harm Reduction: The VicMeth Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,270,774.00
Summary
The Victorian methamphetamine epidemic has received extensive media coverage highlighting the devastating impact of the drug and resultant public concern. We will follow up a cohort of 800 methamphetamine smokers from metropolitan and regional Victoria bi-annually for a period of 5 years to determine the natural history of methamphetamine use to inform optimal intervention strategies and arrest the increases in harm observed in Victoria recently.