Central Neural Mechanisms Underlying The Effect Of Endocannabinoids On Body Weight
Funder
National Health and Medical Research Council
Funding Amount
$377,793.00
Summary
Obesity and its associated pathologies of cardiovascular and respiratory disease, stroke, predisposition to some cancers and infertility in women no longer needs to be justified as a major health issue in modern societies. In fact it is quickly becoming recognised as the major threat to world health. Recently, the anecdotal evidence for increased food intake, particularly the craving of high carbohydrate, high sugar foods, associated with the use of marijuana has been put into a therapeutic cont ....Obesity and its associated pathologies of cardiovascular and respiratory disease, stroke, predisposition to some cancers and infertility in women no longer needs to be justified as a major health issue in modern societies. In fact it is quickly becoming recognised as the major threat to world health. Recently, the anecdotal evidence for increased food intake, particularly the craving of high carbohydrate, high sugar foods, associated with the use of marijuana has been put into a therapeutic context. Specifically a cannabinoid receptor antagonist, rimonabant (currently undergoing trials as Accomplia) has become a central player in the race for an obesity therapy because of its effects in blocking the brain receptors that would normally respond to cannabinoid like compounds in the brain that tend to increase food intake. Despite the trials that are underway in Europe and the USA many of the central actions of the naturally occurring cannabinoids in the brain, the so-called endocannabinoids are very poorly understood. This series of experiments utilizing the best technologies available will address basic questions relating to the brain pathways involved and even the extent to which weight loss associated with the administration of these drugs to rats and presumably humans is dependent on the reduction of food intake or the burning of energy in a process called thermogenesis. These are essential pieces of information if this type of compound is to be considered as a serious contender in the search for an obesity therapyRead moreRead less
Standardisation Of Prepulse Inhibition Of The Startle Reflex For Pharmacological And Interspecies Comparisons
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
People and other animals startle when they here a sudden loud sound. How much one startles depends in part on how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is different. There are genetic differe ....People and other animals startle when they here a sudden loud sound. How much one startles depends in part on how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is different. There are genetic differences in ski slopes as well. The size of the startle reflex can also be reduced by preceding the startling sound with a quiet stimulus a few tens of milliseconds before the startling stimulus. This is known as prepulse inhibition of the startle reflex or PPI for short. There is much interest in PPI, because it differs in people with certain mental illnesses, such as schizophrenia or post-traumatic stress disorder, and certain neurological illnesses, such as Huntington's chorea. It is also affected by drugs, including stimulants, stress hormones, and cannabis. In almost all the hundreds of experiments on PPI the effect of the prepulse on the response to a startling stimulus is measured at only one startling stimulus loudness. This loudness can be at very different parts of the ski slope for different people or other animals: it may be in the steep slope for one person, well into the plateau for another, or even at the bottom of the ski slope below the threshold in others. The effect of PPI is very different depending on what part of the ski slope the loudness represents. A lack of consistent effects in the literature on PPI by drugs and genetics is explained by this difference. Experiments are planned that will investigate the effect of drugs that are similar to those that treat schizophrenia, stress hormones and cannabis on the effect of prepulses on the whole ski slope. This procedure will provide the consistency in results so far absent.Read moreRead less
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.
My research is focused on understanding the aetiology of brain disorders. I am interested in the interaction of genetic and environmental factors in the development of these disorders. In particular, I will evaluate the validity of rodent models for schizophrenia and Alzheimer’s disease and investigate the therapeutic potential of the endocannabinoid system for both disorders and whether environmental enrichment (e.g. physical exercise) can have beneficial effects in these models.
This is an application for reappointment as a Principal Research Fellow. My primary area of research is preclinical studies of addiction, with a particular emphasis on relapse. I am increasingly engaged in translational studies.
Salt (sodium) is an essential electrolyte. Our convincing and complementary findings provide compelling evidence for a link between evolutionarily ancient “instincts” and substance abuse. This proposal is translational, including studies in opiate dependent humans. Our studies will establish how and where in the brain endogenous opioids are implicated in the gratification of salt appetite, how salt appetite is altered in opiate dependency and if salt appetite recovers following opiate withdrawal
Determining Neuronal Connections Involved In Parkinson's Disease And Cocaine Addiction
Funder
National Health and Medical Research Council
Funding Amount
$343,300.00
Summary
Addictive behaviours in response to cocaine use and fine motor coordination that is affected in Parkinson's disease are both controlled by the same type of cells/neurons, i.e., dopamine neurons. However, the circuitry of these neurons varies from where they originate and the type of connections they make. By understanding the neuronal circuitry of these two circuitries in concert we will be able to gain important insight into their roles in adaptive and pathological brain function.
Shaken Baby Syndrome: Characterization Of A Model And Evaluation Of Novel Pharmacological Therapies
Funder
National Health and Medical Research Council
Funding Amount
$412,460.00
Summary
Shaken baby syndrome is a form of traumatic brain injury in infants less than 2 years of age. It results in death in 10-40 % of cases, and neurological problems in survivors. No treatment exists largely because there is no well characterized model of the syndrome that replicates the human situation. This study will fully characterize our newly developed model of shaken baby syndrome and examine the effectiveness of a novel interventional strategy targeting brain swelling.
Unraveling The Neural Circuitry Of Context-induced Relapse To Alcohol Seeking After Punishment-imposed Abstinence
Funder
National Health and Medical Research Council
Funding Amount
$528,016.00
Summary
Alcohol use disorder (alcoholism) causes significant social and economic costs to Australian society. Alcoholism is a brain disease, and relapse during abstinence is the main problem in successful treatment. In this project, we use an animal model of relapse to alcohol seeking after abstinence imposed by a negative consequence (punishment). This project will identify brain regions which can be targeted in future clinical studies in human alcoholics.
Studying The Interaction Of Reelin Deficiency And Environmental Factors In The Development Of Schizophrenia Using Animal Behavioural Models
Funder
National Health and Medical Research Council
Funding Amount
$438,695.00
Summary
Schizophrenia is caused by an interaction of genetic predisposition and environmental risk factors such as stress or drug abuse. Reelin is a protein involved in the normal development of the brain but its levels are markedly reduced in schizophrenia. We will use mice with low levels of reelin in their brain and assess the effect of environmental stress and drugs of abuse. These studies could elucidate gene-environment interaction in schizophrenia and lead to new treatment strategies.