Rationale: Rats reared in social isolation from weaning show prepulse inhib
ition (PPI) deficits which are thought to model the sensorimotor gating def
icits seen in schizophrenia and other psychiatric disorders. However, recen
t studies have questioned the robustness of this paradigm. Objective: The e
xistence of a substantial dataset generated over 4 years in our laboratory
has allowed the investigation of the robustness and reliability of the proc
edure under a variety of environmental conditions. The effects of atypical
antipsychotics (clozapine, olanzapine and risperidone) under different expe
rimental conditions are also reported. Method: At weaning, Hooded Lister pu
ps were singly (isolates) or group (n = 5) housed (grouped). Eight weeks la
ter, the startle and PPI response of isolates and grouped rats was investig
ated using conditions of fixed inter-stimulus interval (ISI) (pulse = 110 d
B/50 ms; prepulse = 80 dB/30 ms; ISI = 100 ms) or variable ISI conditions (
same pulse and prepulse intensities/durations; ISI = 30, 100, 300 ms). Loco
motor activity (LMA) prior to and following PPI testing was also investigat
ed. Results. Isolation-induced deficits in PPI were demonstrated in ten sep
arate cohorts, reared in three different buildings. Only one cohort demonst
rated weakening of the PPI-deficit which precluded further studies. In one
cohort, the PPI response remained stable over the course of six PPI exposur
es. PPI was unaltered by daily handling, re-socialisation and LMA testing.
Startle and PPI were not correlated, nor was LMA correlated to PPI or start
le. Isolation-induced deficits were attenuated by clozapine (5 mg/kg SC), o
lanzapine (3 mg/kg SC) and risperidone (1 mg/kg IP) under variable ISI cond
itions but not by clozapine (2.5-7.5 mg/kg SC) or olanzapine (0.3-3 mg/kg S
C) under fixed ISI conditions. Conclusion: Isolation-rearing produces robus
t and reliable PPI deficits which are reversed by atypical antipsychotics.