Handling Prevents and Reverses Cognitive Deficits Induced by Sub-Chronic Phencyclidine in a Model of Schizophrenia in Rats
Katie Landreth, Matthew Burgess, Linzi Watson, Jarred Lorusso, Ben Grayson, Michael K Harte, Joanna C. Neill
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study (two experiments) |
|---|---|
| Population | Adult female Lister Hooded rats |
| Intervention | sub-chronic phencyclidine (scPCP) |
| Dose | 2 mg/kg, i.p. twice daily for seven days |
| Duration | Handling for two weeks; NOR testing at two, four, five, and seven weeks post-handling/dosing |
| Measures | Novel object recognition (NOR) task with one-minute and six-hour inter-trial intervals (ITI) |
| Key findings | Handling prevented delay-induced novel object recognition deficits and both prevented and reversed sub-chronic phencyclidine-induced deficits in rats. PCP-control animals failed to discriminate novelty, whereas PCP-handled animals discriminated significantly, suggesting environmental enrichment may be a viable treatment approach for cognitive impairments associated with schizophrenia. |
Abstract
Treatments for schizophrenia are not effective in ameliorating cognitive deficits. Therefore, novel therapies are needed to treat cognitive impairments associated with schizophrenia (CIAS), which are modelled in rats through administration of sub-chronic phencyclidine (scPCP). We have previously shown that enrichment via voluntary exercise prevents and reverses impairments in novel object recognition (NOR) in this model.The present study aimed to investigate if handling could prevent delay-induced NOR deficits and prevent and reverse scPCP-induced NOR deficits.Two cohorts of adult female Lister Hooded rats were used throughout. In experiment one, handling (five minutes/day, five days/week for two weeks), took place before scPCP administration (2mg/kg, i.p. twice daily for seven days). NOR tests were conducted at two, four, and seven weeks post-handling with a one-minute inter-trial interval (ITI) and at five weeks post-dosing with a six-hour ITI. In experiment two, animals were handled after scPCP administration and were tested immediately in the one-minute ITI NOR task and again at two weeks post-handling.In both handling regimens, the PCP-Control groups failed to discriminate novelty, conversely the PCP-Handled groups significantly discriminated in this task. In the 6h ITI test, Vehicle and PCP-Controls failed to discriminate novelty; however, the Vehicle and PCP-Handled groups did significantly discriminate.Handling rats prevented the delay induced NOR deficits and prevented and reversed scPCP-induced deficits in NOR. These findings add to evidence that environmental enrichment is a viable treatment for cognitive deficits in animal tests and models of relevance to schizophrenia, with potential to translate into effective treatments for CIAS.