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
Noradrenaline Transporter Dysfunction In Neural Circulatory Disorders: Clinical, Molecular And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$510,870.00
Summary
We will investigate the clinical relevance of noradrenaline transporter (NET) dysfunction and its molecular and genetic regulation in (1) essential hypertension, (2) postural tachycardia syndrome where the heart rate increases abnormally when the patient assumes an upright position and (3) syncope where subjects experience recurrent blackouts. In a therapeutic approach, we will explore whether NET inhibition can reduce the number of episodes and alleviate the symptoms associated with syncope.
Enhancing Extinction Of Alcohol-Predicitve Stimuli Through Modulation Of Noradrenergic Signaling
Funder
National Health and Medical Research Council
Funding Amount
$374,508.00
Summary
A major obstacle for alcohol-abuse treatment is the high risk of relapse and stimuli previously paired with alcohol use contribute importantly to this risk. Reducing the ability of such stimuli to trigger alcohol-seeking behaviors could significantly improve treatment outcomes. The experiments in the current proposal will develop both behavioral and pharmacological strategies for improving extinction learning with the long term goal of reducing the ability of stimuli to elicit alcohol-seeking.
Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.