Set-up of a System to Reliably Measure the Startle Response in Marmoset Monkeys; Application in Animal Models of Anxiety and Psychosis

摘要

The acoustic startle response is a reflex motor response elicited by a sudden loud sound. In two psychiatric disorders, the startle reflex is altered. Normally, the startle response is decreased appreciably when a low intensity sound stimulus is given shortly before the startle eliciting stimulus. This prepulse inhibition of the startle is nearly absent in patients suffering from schizophrenia. In addition, the startle response is increased during periods of anxiety. In this study, a system is described by which the acoustic startle response in marmoset monkeys may be recorded in a reliable way. In using this system, it could be shown that marmosets possess a pre-pulse inhibition (PPI) of the ASR, similar as in other species. Furthermore, it was shown that a fear potentiation of the startle response may be elicited in the marmoset. Potentially, this system may be used for testing anti-psychotic or anxiolytic activity of drugs in primates. In this study, a series of drugs with a known activity on PPI or fear potentiation of the ASR was tested to validate the system. The effects of Buspiron and Diazepam were tested as examples of drugs with a known anxiolytic effect. In addition, Fluvoxamine and Haloperidol were used in these experiments. Amphetamine, Ketamine and Haloperidol were used as drugs to affect the PPI; in these experiments Diazepam was used as a negative control. These experiments were performed in a randomized, cross-over design. In the fear potentiated startle experiments, four animals were used. They received, following a training period to establish a stable baseline fear potentiation, three dose levels of each of the drugs. In addition, the animals were injected with saline S times spread evenly over the total duration of the experiment to test the stability of the baseline fear potentiation. The four animals used in the PPI group were subjected to a similar dosing schedule.