Inheritance of dopaminergic phenotypes in congenic strains of C3H/ mice and their relationships in a novel method of prepulse inhibition analysis

[Truncated abstract] Schizophrenia is characterised by a variety of symptoms the aetiology and causes of which are unknown. However, the most enduring hypothesis has been the Dopamine Hypothesis, in the form that some kind of hyperactivity in one or more the central dopamine projection systems may be a cause of at least the positive symptoms of Schizophrenia. An endophenotype that is often used as a model for schizophrenia is a decrease in prepulse inhibition of the acoustic startle reflex (PPI). PPI is useful measure since it is 1) present in all mammalian species, 2) a deficit can be induced by dopamine agonists and attenuated with dopamine antagonists (the standard pharmacological treatment for schizophrenia) and 3) the deficit in PPI appears to exhibit a genetic association in asymptomatic first-degree relatives of people with schizophrenia. The problems with PPI have been that PPI deficits are not unique to the diagnosis of schizophrenia, it is highly variable across species and the selective dopamine receptor effects on PPI have been shown to vary between species and laboratories, mostly due to the lack of truly selective receptor ligands. Recent interest in the genetics of PPI and schizophrenia has lead to an increasing use of mice in PPI research. These studies show that PPI measures in mice are quite different from rats, from which most of the neurobiology and pharmacology of PPI have been derived. One issue in cross-species cross-strain comparisons has been the lack of standardised methodology that can adequately account for differences between strains and species in both the sensitivity to startling stimuli and in the degree of startle produced by stimuli of various intensities.