Background: The main aim of the studies in this thesis is to provide insights into
the neonatal phencyclidine (PCP) induced deficits in male and female rats as a
neurodevelopmental animal model of schizophrenia.
Methods: Both male and female rats were treated with neonatal PCP on postnatal
days (PNDs) 7,9 and 11 or vehicle, followed by weaning on PND 21-22. The rats
were then tested in behavioural paradigms such as novel object recognition, spatial
memory and social interaction in their adolescent and adult stages and were also
tested with acute treatment of typical and atypical antipsychotic agents.
Results: Neonatal PCP treatment (10 & 20 mg/kg in males and 10 mg/kg in
females; once a day for 3 days on PND 7,9 and 11) caused novel object recognition
and spatial memory impairment in male and female rats both in the adolescent
(PND35-56) and in the adult stages (PND>56) (chapter 2) and robust deficits in
social interaction behaviours in the adolescent stage. The SI deficits were observed
in adulthood in female but not in male rats thereby establishing a sex-specific social
behavioural deficit (chapter 3). The object memory and social interaction deficits
induced by neonatal PCP treatment were reversed following acute risperidone but
not haloperidol. Finally, the temporal profile of this treatment regime was
investigated and the male and female animals were tested on PND 190 and PND
365. The animals did not have any challenge dose of PCP during their testing stage.
The result showed that there was significant deficit in object and spatial recognition
memory in both male and female animals at both time points, thereby establishing
enduring deficits.
Conclusion: Given the heterogeneity of the schizophrenic disorder and its complex
aetiology, it is understandably difficult to find animal models that completely mimic
most or all of the symptoms associated with the disorder. However, data from the
studies in this thesis support the use of neonatal PCP as a valid animal model of
cognitive and negative symptoms, and explores the effect of antipsychotics in
understanding the model. Also, in light of the efficacy of neonatal PCP to produce
robust object, spatial memory and social interaction deficits in rats, it appears that
this model may be a useful tool to investigate the potential of novel therapeutic
candidates that may help improve therapy and understand the illness.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/5404 |
| Date | January 2011 |
| Creators | Rajagopal, Lakshmi |
| Contributors | Neill, Joanna C., Harte, Michael K. |
| Publisher | University of Bradford, School of Pharmacy |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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