Reversal of isolation rearing-induced deficits in prepulse inhibition by Seroquel and olanzapine

Abstract

Background: Prepulse inhibition (PPI) of startle provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. PPI deficits observed in schizophrenia patients can be modeled in rats by individual housing from weaning until adulthood. Deficits in PPI produced by isolation rearing can be reversed by antipsychotics.

Methods: We evaluated the ability of Seroquel and olanzapine to reverse the isolation-induced 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 and sometimes increased startle reactivity. Seroquel reversed these deficits without affecting PPI in socially reared controls. Olanzapine (2.5 mg/kg) reversed the isolation rearing-induced PPI deficit and tended to increase basal PPI levels. Both antipsychotics antagonized the isolation rearing-induced increase in startle reactivity.

Conclusions: Isolation rearing produces deficits in sensorimotor gating in rats that are reversible by atypical antipsychotics, and may therefore aid in identifying new treatments for schizophrenia.