Acute and chronic LSD effects on rat startle: data supporting an LSD--rat model of schizophrenia

Animal models of human schizophrenia using LSD and related hallucinogens have been challenged on several grounds. One compelling argument against the LSD model is that while schizophrenia can be chronically debilitating, animal and human effects of LSD exhibit behavioral tolerance following chronic administration. The present study tested the effects of acute and chronic LSD on measures of rat startle, a widely used behavioral measure of reactivity and habituation. The results suggest that behavioral tolerance after chronic LSD administration is incomplete, with tolerance exhibited to the acute impairment of habituation but potentiation of startle magnitude on both the first response and the first block of 30 trials. These results are interpreted as supporting the viability of LSD as a model for one or more of the group of schizophrenias.