The role of peroxinitrite in depression

Nitric oxide (NO) is a gaseous messenger molecule involved in the regulation of signalling of a number of neurotransmitter systems, including serotonin and dopamine, which are systems underlying the neurochemical basis of mood and emotion.

NO is also involved in cellular damage by forming the peroxynitrite (-ONOO) radical when combined with the superoxide anion, generating oxidative and nitrosative stress in the brain. A number of studies indicate that oxidative and nitrosative stress is implicated in neuropsychiatric disorders such as major depression. Our laboratory works with novel compounds that potently scavenge the –ONOO radical, which we have shown to be effective in animal models of Parkinson’s disease, a neurodegenerative disorder where oxidative and nitrosative stress are strongly implicated. This project will probe the involvement of the  –ONOO radical in the neuropsychiatric disorder, depression, testing the hypothesis that –ONOO scavenging will positively influence depression-related behaviours in animal models of depression. The project will employ pharmacological tools to scavenge –ONOO and to probe the serotonergic neurotransmitter system. Skills learned will include an introduction to mouse behavioural analyses used in depression research, such as the forced swim test and measures of anhedonia, neuropharmacologial techniques to probe the serotonin system, and analyses of oxidative and nitrosative stress by Western blotting techniques.

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