Genetic differences in startle gating-disruptive effects of apomorphine: evidence for central mediation

Strain differences in sensitivity to dopamine agonist-induced disruption of prepulse inhibition (PPI) may be a useful model for the genetics of PPI deficits in neuropsychiatric disorders. Compared with Long-Evans (LE) rats, Sprague-Dawley (SD) rats are more sensitive to the PPI-disruptive effects of the DA agonist apomorphine. The authors tested the hypothesis that this strain difference reflects brain function rather than peripheral physiology. Significant SD > LE PPI-disruptive effects of apomorphine were observed despite equal apomorphine levels in SD and LE rats in forebrain regions that regulate PPI. SD > LE PPI-disruptive effects of apomorphine were also independent of peripheral versus central route of administration. This model for PPI genetics is sensitive to differences in central rather than peripheral substrates.