Brain And Skin Blood Flow: New Animal Model For Understanding Psychiatric Disorders And Evaluating Psychotropic Agents
Funder
National Health and Medical Research Council
Funding Amount
$874,840.00
Summary
We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-bloo ....We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-blood-vessels message reaches the spinal cord. The pathway involves the amygdala, a forebrain region important in emotional expression and the raphe nuclei in the medulla oblongata. Drugs which affect psychological function also effect skin blood flow. Ecstasy, the street drug used to induce euphoria also constricts the skin vessels, and, sadly, the body temperature may increase so much that death ensues. Ecstasy vigorously constricts the skin blood vessels in rabbits, and temperature increases. Ecstasy is thought to act on serotonin-containing nerve cells in the brain, releasing serotonin (5-HT) onto special 5-HT2A receptors. Activation of these receptors affects both psychological function and skin blood flow. Modern drugs used to treat schizophrenia, so called atypical antipsychotics like clozapine and olanzapine, are thought to act as antagonists at 5-HT2A receptors in the brain. We were thus very excited when we discovered in our rabbit model that clozapine reverses the skin vasoconstriction induced by ecstasy. This means that we have specific hypotheses concerning the actual brain pathways and neurotransmitters whereby ecstasy and clozapine exert their effects on skin blood flow. Elucidating these pathways in rabbits and rats will provide solid knowledge concerning the mechanism of action of the atypical antipsychotics, and it may well prove possible to use our animal model to predict whether proposed new antipsychotic agents will be therapeutically effective.Read moreRead less
Ecstasy use is growing faster throughout the world than than any other drug of abuse. United Nations figures from 2003 show that it is used by more individuals than the combined total of cocaine and heroin users. Australia has the highest per capita use of 'Ecstasy' in the world with rates twice those of North Americal and Europe. As a result of this we also have a high rate of adverse effects. These can be immediate, and lead to death, or long term leading to brain damage and psychopathologies. ....Ecstasy use is growing faster throughout the world than than any other drug of abuse. United Nations figures from 2003 show that it is used by more individuals than the combined total of cocaine and heroin users. Australia has the highest per capita use of 'Ecstasy' in the world with rates twice those of North Americal and Europe. As a result of this we also have a high rate of adverse effects. These can be immediate, and lead to death, or long term leading to brain damage and psychopathologies. So far, no studies have been conducted,anywhere in the world, which have objectively examined the medical effects of 'ecstasy' in the dance clubs where it is used. Because of this, there is a lot of speculation on whether the animal based or hospital based studies are valid and relate to normal recreational use of this drug. This has led to a degree of suspicion by users and health professionals as to the medical problems claimed to be associated with the drug. This project extends a pilot study we undertook which has highlighted that in a recreational setting it is likely that specific individuals are susceptible to damage by 'ecstasy'. The purpose of this project is to examine this in detail, and identify who, and why some young persons are at risk of immediate life threatening outcomes from 'ecstasy' use or may develop brain damage later. The intended outcome is to provide clear evidence of adverse effects and why they occur. This evidence may be used to improve harm minimisation and treatment programs.Read moreRead less
Biological And Psychological Health Indices Of Ecstasy/polydrug Users: Testing The Bioenergetic Stress Model
Funder
National Health and Medical Research Council
Funding Amount
$344,015.00
Summary
Use of Ecstasy is increasing in both Australia and the United Kingdom, and is related to poorer psychological and mental functioning in the long-term, suggesting Ecstasy use negatively impacts human physiology producing deficits in aspects of mental functioning. This project aims to assess the effect of weekend use and lifetime use of ecstasy upon measures of physiology and psychology. Findings from these studies may contribute to strategies to reduce the harm associated with Ecstasy use.
Neural Mechanisms Mediating Inhibitory Influences Of Hyperthermia, Fever And Age On Water Intake
Funder
National Health and Medical Research Council
Funding Amount
$324,125.00
Summary
An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand ....An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand mechanisms by which the thirst mechanism in the brain is supressed. We have observed that a high body temperature may have an inhibitory influence on thirst in rats, and it is also known that thirst mechanisms are depressed in elderly people. If we can identify the regions of the brain that are involved and the mechanisms underpinning this reduced thirst, then it will be possible to identify and alert people at risk and to design strategies to prevent dangerous levels of dehydration occurring due to reduced thirst, particularly in the elderly. This may also apply to to people who may be working or undertaking vigorous exercise in hot weather or taking certain medications.Read moreRead less
The Role Of Neuropeptides In The Acute And Long-term Effects Of MDMA, Methamphetamine And GHB
Funder
National Health and Medical Research Council
Funding Amount
$472,321.00
Summary
The widespread use of 'party drugs' (ecstasy, methamphetmaine and GHB) is a major health issue in Australia. We propose a novel hypothesis that key acute and long-term effects of these drugs may involve an action on the neuropeptide oxytocin. A number of experiments are planned to test this hypothesis. The findings from this project will be used to better understand and to explore novel treatments for people who suffer problems as a result of using these drugs.
Investigations Of Neural Pathways For Heat Loss And Heat Gain In Thermoregulation And Fever
Funder
National Health and Medical Research Council
Funding Amount
$349,486.00
Summary
This project aims to map the nerve pathways in the brain that participate in the regulation of body temperature in the laboratory rat. The area of the brain that will be studied is the hypothalamic region. We will determine how this region influences the constriction of blood vessels in the skin to reduce heat loss when an animal is exposed to a cool environment, or when it exhibits a fever in response to a bacterial infection. As well, we will compare the nervous pathway that controls the gener ....This project aims to map the nerve pathways in the brain that participate in the regulation of body temperature in the laboratory rat. The area of the brain that will be studied is the hypothalamic region. We will determine how this region influences the constriction of blood vessels in the skin to reduce heat loss when an animal is exposed to a cool environment, or when it exhibits a fever in response to a bacterial infection. As well, we will compare the nervous pathway that controls the generation of heat from fat tissue in response to cold or fever with those controlling blood flow to the skin. These nervous pathways may be critical for maintaining correct body temperature during general anaesthesia, infections or in the aged subjected to temperature extremes. Thus, they are of importance in the health and well-being of much of the population.Read moreRead less
Brain Pathways For Neurally-mediated Fever: From Vagal Afferent To Sympathetic Output To Brown Adipose Tissue Via Brain
Funder
National Health and Medical Research Council
Funding Amount
$405,223.00
Summary
Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins ....Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins (cytokines) are released. The cytokines enter the blood stream and are transported to the brain. Recently, the existence of another signalling pathway has been demonstrated. The pathway is via a special peripheral sensory nerve, the abdominal vagal sensory nerve. However, special neural pathways in the brain have not yet been clarified, even though several neural relay stations have been proposed. To elucidate neural pathways transmitting information of infection to the brain, both input and output of the pathway need to be specified. Specific outputs other than body temperature have not been determined, so far. I have recently developed a new reflex model, in which I focus on sympathetic nerves supplying the specialised fat tissue as an output as well as the vagus sensory nerve as an input. The fat tissue, brown adipose tissue (BAT), generates heat. When the vagus sensory nerve is stimulated electrically, BAT sympathetic nerve is activated. We were very exited when we discovered the potency of the combination in our rat model. We are now ready to elucidate brain pathways for neurally-mediated fever, using our new reflex model. Signalling to the brain via the nervous system is faster than via the blood stream, and thus must be very important for the earliest phase of fever. Understanding the neural pathways by which the brain perceives peripheral infection and triggers fever may promote beneficial aspects of the acute-phase immune reaction.Read moreRead less