Microinfusion of the non-competitive N-methyl- d-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats does not affect latent inhibition and prepulse inhibition, but increases startle reaction and locomotor activity

Abstract

Latent inhibition (the retarded conditioning to a stimulus following its repeated non-reinforced pre-exposure) and prepulse inhibition (the reduction in the startle response to an intense acoustic stimulus when this stimulus is immediately preceded by a prepulse) reflect cognitive and sensorimotor gating processes, respectively, and are deficient in schizophrenic patients. The disruption of latent inhibition and prepulse inhibition in the rat is used as an animal model for the attentional deficits associated with schizophrenia. The present study tested the extent to which latent inhibition and prepulse inhibition, startle reaction and locomotor activity in the open field were affected by infusing the non-competitive N-methyl- d-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats. We used the same dose of MK-801 (6.25 μg/0.5 μl per side) previously found to be effective in the disruption of prepulse inhibition when infused into the dorsal hippocampus of Sprague–Dawley rats [Bakshi V. P. and Geyer M. A. (1998) J. Neurosci. 18, 8394–8401; Bakshi V. P. and Geyer M. A. (1999) Neuroscience 92, 113–121]. Bilateral infusion of MK-801 into the dorsal hippocampus did not disrupt latent inhibition. Furthermore, in contrast to previous studies, we failed to find a significant disruption of prepulse inhibition after MK-801 infusion into the dorsal hippocampus, although MK-801 infusion was effective in increasing the startle amplitude as well as locomotor activity in an open field. From our results, we suggest that N-methyl- d-aspartate receptor-mediated processes within the dorsal hippocampus are not necessary for the normal maintenance of the attentional processes reflected by latent inhibition and prepulse inhibition.