Effects of typical and atypical antipsychotics on prepulse inhibition and latent inhibition in chronic schizophrenia

Background: Prepulse inhibition and latent inhibition are the two animal paradigms currently dominating neuropharmacological research on attentional deficits in schizophrenia. Both paradigms have been shown to have a reasonable amount of face, predictive, and construct validity, but responsiveness to typical and atypical antipsychotics differs between the two, as indicated by animal and human studies. The relationship between the paradigms in schizophrenic patients is still unclear. Methods: We tested prepulse inhibition and auditory latent inhibition in a sample of 33 chronic schizophrenic patients medicated either with atypical (n = 17) or typical (n = 16) antipsychotics. Results: Latent inhibition was found to be intact in both patient groups. Prepulse inhibition was intact in the group receiving atypicals, but deficient in the group receiving typicals (at 60 msec lead interval condition). Conclusions: The direct comparison supports the hypothesis that atypical and typical antipsychotics have different effects on prepulse inhibition than on latent inhibition in schizophrenic patients; however, the results may also be explained by a greater sensitivity of the prepulse inhibition method. Because it is crucial to understand why there are considerable differences between the two paradigms and between human and animal studies, research should focus more strongly on comparative approaches.