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
Attentional Effects On Prepulse Inhibition Of The Acoustic Startle Reflex In Patients With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$278,625.00
Summary
People suffering from schizophrenia exhibit differences from healthy people in the startle reflex, which is a blink of the eyes when a sudden loud sound occurs. Normally, this reflex is reduced in size when a quiet sound occurs a few milliseconds before the startling sound, but this prepulse inhibition of the startle reflex or PPI does not occur to the same degree in people with schizophrenia. The underlying causes of this reduction in PPI in patients with schizophrenia is not known. The most co ....People suffering from schizophrenia exhibit differences from healthy people in the startle reflex, which is a blink of the eyes when a sudden loud sound occurs. Normally, this reflex is reduced in size when a quiet sound occurs a few milliseconds before the startling sound, but this prepulse inhibition of the startle reflex or PPI does not occur to the same degree in people with schizophrenia. The underlying causes of this reduction in PPI in patients with schizophrenia is not known. The most commonly accepted theory is that it reflects a deficit in a basic sensorimotor gating function which could underlie a variety of attentional abnormalities observed in schizophrenia. However, our data indicate that patients exhibit more PPI when they ignore the prepulse stimuli. We wish to test the hypothesis that alterations in PPI in schizophrenic patients are secondary to abnormalities in attention. This is significant because the theory can point to a specific cognitive deficit associated with schizophrenia. We have also found that patients treated with some kinds of antipsychotic medications (the newer atypical antipsychotic medications) do not show reductions in PPI, but patients treated with older types of antipsychotic drug do show reductions in PPI. We intend to investigate the effects of different types of antipsychotics on attentional modulation of PPI. This is significant because it may indicate that patients with a specific kind of cognitive impairment may show improvement with a specific type of medicine. Our data suggests that chronic cannabis use may associated with differences in the startle reflex and in PPI. Understanding how such cannabis use alters PPI may provide insights into why so many people with schizophrenia regularly abuse cannabis.Read moreRead less