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Title: Behavioural and neurochemical changes in the isolation-reared rat following pharmacological challenge of the glutatamergic signalling system
Author: Jones, Caitlin Angharad
ISNI:       0000 0004 2737 1629
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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The post-weaning social isolation reanng rat model utilises early-life, environmental adversity to mimic the neurodevelopmental aetiology of schizophrenia. The overall aim of this thesis was to investigate behavioural and neurochemical changes associated with this model in to deduce whether manipulation of central glutamatergic pathways could account for some of the 'schizophrenia-like' alterations seen. Results confirmed that postweaning-social isolation rearing during adolescence induced a range of 'schizophrenia-like' behavioural changes in the adult rat. Isolation- rearing from weaning induced locomotor hyperactivity in a novel arena which was reversed by the mGluR2/3 agonist, LY379268, impaired performance in a novel object discrimination task which was selectively reversed by LY379268 and the NMDAR antagonist, memantine, reduced prepulse inhibition of the acoustic startle response and reduced conditioned emotional learning in a contextual fear conditioning paradigm. Neither drug had an effect on PPI or emotional processing deficits. Acute systemic administration of PCP to adult rats, with the exception of worsening PPI deficits, had no effect on isolation-rearing induced behavioural changes. Discrete administration of memantine into the mPFC of isolation-reared rats by reverse in vivo microdialysis reduced impairments in novel object discrimination and was accompanied by an apparent increase in extracellular dopamine compared with that in vehicle-treated rats. No task- related changes in extracellular amino acids were seen in either group, thus implying a dopamine-dependent mechanism of action of the drug that warrants further investigation. From these results, it could be hypothesised that dampening ex citatory activity in key brain regions either by voltage-dependent blockade of postsynaptic NMDA receptors or via the activation of presynaptic mGluR2/3 receptors, may have beneficial effects on cognitive performance in this animal model.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available