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
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.
Interaction Between Symptoms Of Brainstem Disturbance, Sensory Disturbances And Pain In Migraine
Funder
National Health and Medical Research Council
Funding Amount
$165,509.00
Summary
Migraine affects about 18% of women and 6% of men across their lifespan and usually peaks during the most productive years of life. Although serious neurological effects of migraine are rare, some sufferers are left with permanent physical disability after attacks of migraine-related stroke. More common are debilitating side effects of medication, and the psychological and social disruption of experiencing recurrent attacks of migraine. Apart from the pain and distress experienced during migrain ....Migraine affects about 18% of women and 6% of men across their lifespan and usually peaks during the most productive years of life. Although serious neurological effects of migraine are rare, some sufferers are left with permanent physical disability after attacks of migraine-related stroke. More common are debilitating side effects of medication, and the psychological and social disruption of experiencing recurrent attacks of migraine. Apart from the pain and distress experienced during migraine, recurrent headaches are responsible for considerable health care costs and lost productivity. Thus, there are important economic and social reasons for developing new treatments, particularly treatments that reduce susceptibility to recurrent attacks. This project aims to investigate interactions among symptoms of migraine (head pain, nausea, and changes in facial blood flow), so that the sequence of symptom development can be studied systematically. We will induce motion sickness (which provokes nausea and many other symptoms of migraine), and then study the effects of head pain and strong sensory stimulation. We expect that migraine sufferers will report stronger symptoms and show greater physiological changes to these stimuli, either alone or in combination, than people who rarely suffer from headache. One of the most commonly recognized triggers of migraine is psychological stress. The aim of the second part of this project is to determine whether a substance released during stress (noradrenaline) heightens inflammation in scalp blood vessels, thus increasing the likelihood of migraine. We hope that this approach will help to identify the basis of the abnormality which increases susceptibility to migraine, so that it can be targeted for treatment.Read moreRead less