Role Of Brain Serotonin In Animal Models Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$175,550.00
Summary
There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors' (keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional 'typical' antipsychotics in terms of efficacy an ....There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors' (keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional 'typical' antipsychotics in terms of efficacy and side-effect profile. Typical antipsychotic drugs act mainly through blockade of receptors for a brain chemical called dopamine. Atypical drugs appear to have additional actions, in particular blocking the effect of serotonin in the brain. This evidence is mostly circumstancial, relying to a large extent on biochemical analysis of brain regions and 'receptors' on which antipsychotics MAY act. It is currently unclear exactly how and where in the brain changes in serotonin activity influence behavioural processes causing schizophrenia. It is also unclear how and where typical and atypical antipsychotic drugs interact with the role of serotonin in schizophrenia. In this project we intend to inactivate specific parts of the serotonin system of otherwise intact, freely moving rats. Using behavioural observation methods relevant for schizophrenia, we will analyze if and how these interventions influence the behaviour of these rats. The results can have important implications for our fundamental understanding of the involvement of serotonin in the brain in schizophrenia.Read moreRead less
Panic Disorder: Neurobiology And Mechanisms Of Cardiac Risks
Funder
National Health and Medical Research Council
Funding Amount
$414,375.00
Summary
Some people are subject to episodes of recurring, often inexplicable anxiety which are very unpleasant and accompanied by physical symptoms such as sweating, palpitations, tremor and a sensation of suffocation. Recurring attacks over a period of months, or years, forms the basis for the diagnosis of panic disorder. It has until recently been felt that although panic disorder was distressing and disabling, it did not constitute a risk to life. Sufferers often fear that they have heart disease, be ....Some people are subject to episodes of recurring, often inexplicable anxiety which are very unpleasant and accompanied by physical symptoms such as sweating, palpitations, tremor and a sensation of suffocation. Recurring attacks over a period of months, or years, forms the basis for the diagnosis of panic disorder. It has until recently been felt that although panic disorder was distressing and disabling, it did not constitute a risk to life. Sufferers often fear that they have heart disease, because of the nature of their symptoms, but have been reassured that this is not the case. Recent epidemiological studies, however, indicate that there is an increased risk of heart risk in patients with panic disorder. Our hypotheses in this research are as follows: That panic disorder is characterised by increased release of the brain chemical messenger, serotonin, which is reversed by drug treatment with the most widely used class of drugs for this disorder, selective serotonin reuptake blockers That changes in an automatic stimulatory part of the nervous system, has primary importance in the disorder, in both genetically predisposing to panic disorder, and in mediating heart risk. That weight gain during therapy, a very common problem, is due to inhibition of brain serotonin release. We will test all these propositions using state of the art clinical scientific methods. Panic disorder has an important cardiological dimension which needs to be better understood for cardiac protection to be achieved in panic disorder patients. Our study of the mechanisms of cardiac risk should provide this. We will also provide very direct, valid measurements of chemical messenger release in the brain of panic disorder sufferers, using our unique methods. These should give a new understanding of the brain chemistry abnormalities of panic disorder, and the mechanism of action of the selective serotonin reuptake inhibitors.Read moreRead less