Effects of subchronic d-amphetamine on prepulse and gap inhibition of the acoustic startle reflex in rats.

Prepulse inhibition of the startle reflex has been used as an animal model for information processing deficits found in some types of schizophrenia. These deficits may be mediated by hypersensitive dopaminergic systems. In the present study, the effects of subchronic d-amphetamine administration [2 mg/kg intraperitoneally (IP)] on prepulse and gap inhibition of the startle reflex were compared to the effects of acute amphetamine and saline administration on startle inhibition. Results of three experiments are reported. The first two experiments were used to select prestimulus parameters sensitive to changes in stimulus intensity on the one hand, and prestimulus parameters sensitive to temporal aspects of stimulus processing on the other hand. Because schizophrenics have problems with the temporal sequencing of information, prestimulus inhibition of the startle reflex was expected to be more pronounced when prestimulus processing depended predominantly upon temporal factors. Results supported this hypothesis, although the effects of d-amphetamine were found at near detection threshold duration only. Subchronic amphetamine had no effect on the neuronal mechanisms underlying inhibition of the startle reflex by prestimuli. The results also suggested that a careful selection of duration and intensity of the prestimulus may increase the sensitivity of the prestimulus-startle paradigm for the effects of drugs, for example.