Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in rats

Citation
J. Cilia et al., Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in rats, PSYCHOPHAR, 156(2-3), 2001, pp. 327-337
Citations number
37
Categorie Soggetti
Neurosciences & Behavoir
Journal title
Volume
156
Issue
2-3
Year of publication
2001
Pages
327 - 337
Database
ISI
SICI code
Abstract
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.