Nociceptin/orphanin FQ-NOP receptor signalling and mood regulation: behavioural, pharmacological and neurochemical studies

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Depression is a devastating disease with high incidence and societal cost involving dysfunction of noradrenergic and serotonergic brain circuits. Current antidepressants are not ideal with less than half of the patients treated attaining complete remission using a single antidepressant whilst others exhibit partial, refractory or intolerant responses.

There is a need for novel antidepressants and neuropeptides represent an interesting lead. Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) constitute a novel peptide-receptor system expressed in areas of the brain involved in emotional processing.

The limited number of NOP antagonists available produce antidepressant-like effects in mice and NOP receptor knockouts display antidepressant-like phenotypes. This project is to validate the NOP receptor as an antidepressant target. In vitro assays will be employed to characterize the pharmacological profile of novel NOP antagonists.

In vivo studies in rats and mice will characterize acute and chronic actions of N OP antagonist-induced effects in various models of depression. Mechanistically, interactions between monoamines and N/OFQ-NOP receptor system will be evaluated with reference to monoaminergic pathways, noradrenergic/serotonergicreceptors and monoamine release.

This proposal brings together researchers with expertise both necessary and sufficient for this project which is hoped will provide evidence for NOP antagonists as a novel class of antidepressants.

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UNIVERSITA DEGLI STUDI DI FERRARA

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Via Savonarola 9
FERRARA
Italien

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