Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in rats: an update
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Rats reared in social isolation from weaning show prepulse inhibition (PPI) deficits which are thought to model the sensorimotor gating deficits seen in schizophrenia and other psychiatric disorders. We have previously reported that ten cohorts of Lister Hooded rats reared in isolation showed robust and reliable PPI deficits.
Our methodology differed from those used by others (Weiss and Feldon in Psychopharmacology 156(2–3):305–326, 2001), most notably in the weaning of pups at postnatal day (PND) 28 compared with PND20-22. Since our initial report, we have studied 18 more cohorts weaned at PND28 and one cohort weaned at PND21.
At weaning, male Lister Hooded pups were singly (isolates) or group (n=5) housed (grouped). Eight weeks later, startle and PPI responses of isolates and grouped rats were investigated using conditions of fixed inter-stimulus interval (ISI) (pulse=110 dB/50 ms; prepulse (PP)=75–80 dB/30 ms; ISI=100 ms).
Isolates from 14 of the subsequent 18 cohorts demonstrated PPI deficits, giving an overall success rate of 86% for all 28 cohorts. %PPI ranged from 12 to 26% in the isolates and from 26 to 47% in the grouped for the successful cohorts, compared to 16–30% (isolates) and 19–35% (grouped) for those that failed. Only five out of the 19 subsequent cohorts demonstrated startle hyperreactivity, which was unrelated to PPI response. The isolates from the cohort weaned at PND21 did not show a significant deficit in PPI, suggesting, in our hands at least, a requirement for weaning at PND28.
The data presented here reinforce our original findings that isolation-rearing of Lister Hooded rats provides a viable, non-pharmacological model of impaired PPI.
KeywordsPrepulse inhibition Isolation rearing Schizophrenia Rats
The authors would like to thank Andrew Lloyd for his statistical contribution and Steven Balch for performing a large proportion of the PPI testing.
- Braff DL, Swerdlow NR, Geyer MA (1995) Gating and habituation deficits in the schizophrenia disorders. Clin Neurosci 3:131–139Google Scholar
- Bristow LJ, Landon L, Saywell KL, Tricklebank MD (1995) The glycine/NMDA receptor antagonist, l-701,324 reverses isolation-induced deficits in prepulse inhibition in the rat. Psychopharmacology 118:230–232Google Scholar
- Cilia J, Reavill C, Hagan JJ, Jones DNC (2001) Long-term evaluation of isolation-reared prepulse inhibition deficits in rats. Psychopharmacology 156:327–337Google Scholar
- Day-Wilson KM, Jones DNC, Cilia J, Southam E, Totterdell S (2003) Prefrontal cortex volume loss in rats with isolation rearing-induced deficits in prepulse inhibition of acoustic startle. Program No. 315.3. Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC. OnlineGoogle Scholar
- Duncan EJ, Szilagyi S, Efferen TR, Schwartz MP, Parwani A, Chakravorty S, Madonick SH, Kunzova A, Harmon JW, Angrist B, Gonzenbach S, Rotrosen JP (2003) Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia. Psychopharmacology 167:63–71Google Scholar
- Heidbreder CA, Foxton R, Cilia J, Hughes ZA, Shah AJ, Atkins A, Hunter AJ, Hagan JJ, Jones DNC (2001) Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation. Psychopharmacology 156:338–351Google Scholar
- Hughes ZA, Cilia J, Hughes JL, Savage KM, Shilliam CS, Heidbreder CA, Jones DNC, Dawson LA (2004) Further neurochemical characterisation of the social isolation reared rat model: brain region specific differential responses to the atypical antipsychotic clozapine. Submitted.Google Scholar
- Kelly KBD, O’Callaghan E, Lane A, Larkin C (2003) Schizophrenia: solving the puzzle. Ir J Med Sci 172(1):37–40Google Scholar
- Reavill C, Taylor SG, Wood MD, Ashmeade T, Austin NE, Avenell KY, Boyfiled I, Branch CL, Cilia J, Coldwell MC, Hadley MS, Hunter AJ, Jeffrey P, Jewett F, Johnson CN, Jones DNC, Medhurst AD, Middlemiss DN, Nash DJ, Riley GJ, Routledge, Stemp G, Thewlis KM, Trail B, Vong AKK, Hagan J (2000) Pharmacological actions of a novel high affinity and selective dopamine D3 receptor antagonist, SB-277011-A. J Pharmacol Exp Ther 294:1154–1165Google Scholar
- Rosa MLNM, Silva RCB, Moura-de-Carvalho FT, Brandao ML, Guimaraes FS, Del Bel EA (2003) Non-handling is critical for isolation rearing-induced changes in prepulse inhibition in rats. J Psychopharmacol 17(3):A44Google Scholar
- Swerdlow NR, Braff DL, Geyer MA (2000) Animal models of deficient sensorimotor gating: what we know, what we think we know, and what we hope to know soon. Behav Pharmacol 11(3–4):269–279Google Scholar
- Talamini LM, Ellenbroek B, Koch T, Korf J (2000) Impaired sensory gating and attention in rats with developmental abnormalities of the mesocortex. Implications for schizophrenia. Ann NY Acad Sci 911:486–494Google Scholar
- Van den Buuse M, Garner B, Koch M (2003) Neurodevelopmental animal models of schizophrenia: effects on prepulse inhibition. Curr Mol Med 3:459–471Google Scholar
- Varty GB, Higgins GA (1995) Examination of drug-induced and isolation-induced disruptions of prepulse inhibition as models to screen antipsychotic drugs. Psychopharmacology 122:15–26Google Scholar
- Weiss IC, Feldon J (2001) Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review. Psychopharmacology 156(2–3):305–326Google Scholar
- Weiss IC, Feldon J, Domeney AM (1999) Isolation rearing-induced disruption of prepulse inhibition: further evidence for fragility of the response. Behav Pharmacol 10:139–149Google Scholar
- Wilkinson LS, Killcross SS, Humby T, Hall FS, Geyer MA, Robbins TW (1994) Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition. Neuropsychopharmacology 10:61–72Google Scholar