Metabotropic glutamate receptor modulation of mesolimbic dopamine release: effect of phencyclidine pretreatment modelling schizophrenia (360G-Wellcome-211794_Z_18_Z)

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Schizophrenia is a severely debilitating mental condition, affecting ~0.5% of the population. Current theories suggest a core deficit in cortical glutamate which causes dysregulation of glutamatergic control of dopamine release in nucleus accumbens. In particular phasic (high-frequency) activity, related to attentional processes, rather than tonic (low-frequency) activity, is vulnerable. However, remarkably little is known about mechanisms involved. Phencyclidine (glutamate antagonist), causes changes in people, resembling schizophrenia. In animals, short-term chronic treatment causes behavioural deficits mimicking changes in schizophrenia, providing an animal model for studying causative mechanisms. In clinical trials, type-2 metabotropic glutamate receptors (mGluR2) agonists alleviated psychotic symptoms. In rats they reverse psychomimetic effects of phencyclidine and modulate accumbal dopamine release. We suggest that these processes are dysfunctional in schizophrenia, which accounts, at least in part, for glutamate-dopamine dysregulation. The aim of this study is to use fast cyclic voltammetry in vitro, to characterise the effects of activation of mGluR2 on stimulated accumbal dopamine release, particularly focussing on differences between phasic and tonic stimuli, and assess whether this modulation is disrupted by subchronic phencyclidine pretreatment, modelling schizophrenia. Identifying fundamental mechanism determining glutamatergic modulation of accumbal dopamine function, and dysfunction in model schizophrenia, underpins further research developing novel antipsychotic treatment strategies.

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Grant Details

Amount Awarded 0
Applicant Surname Drury
Approval Committee Internal Decision Panel
Award Date 2018-05-31T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Vacation Scholarships
Internal ID 211794/Z/18/Z
Lead Applicant Miss Tamsin Drury
Partnership Value 0
Planned Dates: End Date 2018-09-22T00:00:00+00:00
Planned Dates: Start Date 2018-07-23T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East Midlands