Selective breeding for deficient sensorimotor gating is accompanied by increased perseveration in rats.

Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating that is deficient in some neuropsychiatric disorders, such as schizophrenia and Tourette's syndrome. Experimentally induced PPI deficits in rats are regarded as endophenotype to study the biological mechanisms and therapeutic strategies of these disorders. We have recently shown that selectively breeding rats for high and low PPI levels, respectively, leads to groups with different PPI performance that remains stable from the second generation on. We here tested whether the low PPI is accompanied by other behavioral deficits. Different spatial and operant learning paradigms were used to assess rats' learning and memory abilities as well as their behavioral flexibility. In the delayed alternation T-maze task the two groups did not differ in task acquisition and working memory. Rats with low PPI showed enhanced perseveration during switching between an egocentric and allocentric radial maze task. Enhanced perseveration was also found in an operant behavioral task, where different demands, i.e. a different number of lever presses for a pellet-reward, were assigned to and switched between two levers of a Skinner box. Rats with low PPI stayed longer at the ineffective lever before switching, thus being less able to adjust their behavior to changing reward values. Additionally, PPI low rats had a higher breakpoint value during a progressive ratio-schedule of reinforcement. Rats selectively bred for low PPI showed some cognitive deficits that are apparent in a number of psychiatric disorders with deficient information processing. Specifically in both, spatial and operant behavioral paradigms, PPI low rats are deteriorated in their ability to modulate behavior based upon new changing information. They may thus provide a non-pharmacological model that can be used to evaluate new therapeutic strategies ranging from pharmacological treatment to functional neurosurgery.