MOLECULAR STRUCTURE-FUNCTION RELATIONSHIPS OF THE NORADRENALINE TRANSPORTER & DRUG ACTION
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmi ....The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmitters, noradrenaline, serotonin and dopamine. Recently, the structures of the transporter proteins have been determined using molecular biology techniques. The focus of this project is to determine the parts of the noradrenaline transporter protein structure that are important in determining its functions, utilising the knowledge that we now have about its molecular structure. This will lead to exciting advances in understanding the function of the noradrenaline transporter and these advances should ultimately lead to the development of more effective antidepressant drugs and of drugs to prevent the effects of psychostimulants such as cocaine.Read moreRead less
Preclinical Investigation Into Novel Therapeutics To Treat Drug Abuse During Adolescence And Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$713,684.00
Summary
To investigate early life drug abuse and its treatment, drug-consumption and seeking behaviour will be examined in adolescent rats. We expect dopamine immaturity during adolescence to be a critical factor in persistence of drug-seeking in adolescence.
Brain Pathways Underlying Vulnerability To Drug Relapse
Funder
National Health and Medical Research Council
Funding Amount
$416,788.00
Summary
Addiction to drugs is a major health and social burden for Australian society. Once addiction is established, prevention of relapse is the most significant obstacle to successful treatment. Unfortunately, efficacious pharmaceutical options to treat relapse are lacking. By employing an animal model of relapse that accurately reflects drug taking in humans the proposed project aims to advance our understanding of the brain mechanism underlying addiction.
Orexin/Hypocretin Receptors In Self-Administration And Stress-Induced Reinstatement Of Ethanol Seeking
Funder
National Health and Medical Research Council
Funding Amount
$538,221.00
Summary
Orexin receptors are novel therapeutic targets implicated in alcohol use disorders. There is little known about how orexin receptors drive ethanol consumption and stress-induced reinstatement. This project provides a unique opportunity to determine the mechanism of action of orexin receptors in alcohol use disorders and devise novel therapeutic strategies to treat alcohol use disorders.
Serotonergic Mechanisms Underlying Impulsivity And Vulnerability For Stimulant Addiction
Funder
National Health and Medical Research Council
Funding Amount
$336,318.00
Summary
There is increasing evidence to suggest that impulsivity, a personality trait associated with an increased tendency for premature actions, may predispose individuals to stimulant addiction. The current study employs a non-invasive brain imaging technique in rats – positron emission tomography (PET) – to investigate the implicated role of serotonin (5HT) in impulsivity thereby providing potentially new insights into neural vulnerability mechanisms underlying stimulant addiction.
I am a neuroscientist, studying fundamental mechanisms related to addiction. A major feature of my research is the neuropharmacological characterisation of potential novel therapeutic strategies to combat drug-seeking behaviour.
Neuropathways And Synaptic Adaptations Underlying Drug Addiction In Central Dopamine Systems
Funder
National Health and Medical Research Council
Funding Amount
$184,812.00
Summary
There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells undergo long-term depression (LTD) and potentiation (LTP) of ....There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells undergo long-term depression (LTD) and potentiation (LTP) of synaptic strength when excitatory inputs to DA cells are stimulated. These findings are important to drug addiction as amphetamine has been shown to block LTD and enhance LTP in brain slices of DA cells. Thus, changes in LTD and LTP by illicit drugs may underlie the conditions necessary for expression of drug-induced behavioural sensitisation, the best-accepted model of drug-craving in human addiction. To date, these studies have all been conducted in brain slices. Therefore, the functional importance of this synaptic plasticity in midbrain DA cells has yet to be shown in terms of changes in DA release in forebrain terminals in the living animal. For the first time we will address this issue by recording DA cell firing activity together with DA release using a newly developed technique that permits DA release to be monitored in the living brain in 'real-time' (100,000 samples-sec). This will allow us to identify the origin (cortical excitatory inputs) and receptor mechanisms that mediate LTP and LTD in DA cells and their effects on DA release. Recording DA cell activity with real-time measurement of DA release will promote a new cutting-edge technology to the Australian Neurosciences. These data will provide 'first of its kind' evidence of the functional anatomy and receptor mechanisms underlying synaptic plasticity in DA neurons associated with repeated drug use and ultimately enhance our basic understanding of the neural mechanisms of human drug addiction.Read moreRead less