REVERSAL OF ISOLATION REARING-INDUCED DEFICITS IN PREPULSE INHIBITIONBY SEROQUEL AND OLANZAPINE

Background: Prepulse inhibition (PPI) of startle provides an operation al measure of sensorimotor gating in which a weak stimulus presented p rior to a startling stimulus reduces the startle response. PPI deficit s observed in schizophrenia patients can be modeled in rats by individ ual housing from weaning until adulthood. Deficits in PPI produced by isolation rearing can be reversed by antipsychotics. Methods: We evalu ated the ability of Seroquel and olanzapine to reverse the isolation-i nduced disruption of PPI. Rats housed for 8 weeks singly or in groups of 3 were tested every 2 weeks after either Seroquel (0, 5.0 mg/kg) or olanzapine (0, 2.5, 5.0 mg/kg). Startle was elicited by 120-dB pulses presented either with or without prepulses (3, 6, or 12 dB above a 65 -dB background). Results: Isolation rearing repeatedly disrupted PPI a nd sometimes increased startle reactivity. Seroquel reversed these def icits without affecting PPI in socially reared controls. Olanzapine (2 .5 mg/kg) reversed the isolation rearing-induced PPI deficit and tende d to increase basal PPI levels. Both antipsychotics antagonized the is olation rearing-induced PPI deficit and tended to increase basal PPI l evels. Both antipsychotics antagonized the isolation rearing-induced i ncrease in startle reactivity. Conclusions: Isolation rearing produces deficits in sensorimotor gating in rats that are reversible by atypic al antipsychotics, and may therefore aid in identifying new treatments for schizophrenia. (C) 1998 Society of Biological Psychiatry.