Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine

Abstract

Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-D-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a..