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.
Investigation Of The Mechanisms Involved In Consolidation Of Memory By Beta 3 Adrenoceptoragonists.
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
The inability to form new memories is a major and increasingly prevalent health problem for an aging population. In addition to aging, the inability to form new memories is associated with serious medical conditions including Alzheimer's Disease and diabetes. Common to these conditions is the inability to consolidate memories. Memories are intact for a short while (30 minutes) after the event to be remembered, but memory does not pass on into permanent storage. We have been able to achieve memor ....The inability to form new memories is a major and increasingly prevalent health problem for an aging population. In addition to aging, the inability to form new memories is associated with serious medical conditions including Alzheimer's Disease and diabetes. Common to these conditions is the inability to consolidate memories. Memories are intact for a short while (30 minutes) after the event to be remembered, but memory does not pass on into permanent storage. We have been able to achieve memory consolidation in a particular learning task, which is not normally remembered, by injection of drugs acting on novel receptors (beta 3 adrenoceptors) in the brain of day old chicks. These drugs mimic the action of noradrenaline at beta-3 adrenoceptors. There are a number of ways in which memory consolidation can be enhanced, and we will compare the effects of beta-3 drugs with other potential drugs acting at other types of noradrenaline receptors. One of the actions of beta-3 agonists is related to the uptake of glucose into cells in the brain. We will investigate whether the mechanism of beta-3 enhancement of memory involves the uptake of glucose in brain tissue and studies in cultures of individual cell types will show us which cells are involved. Although this work is done using young chicks, there is no reason to suppose that the basic memory mechanisms at the level of the nerve cell should be different in birds or mammals. There are distinct advantages to using chicks in this research as they can form a long lasting memory for an experience lasting only 10 seconds, and they will discriminate between different colours as part of their learning. This research is aimed at understanding the processes involved in and influencing memory formation. If we are going to develop drugs to alleviate the cognitive problems of old age and more serious cognitive diseases, we need to understand more about the basic mechanisms of memory formation in the normal animal.Read moreRead less
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