Depression is an extremely common psychiatric condition affecting 10-20% of the population. It is a heterogeneous disorder with patients presenting with one or more core symptoms such as sadness, negative thoughts, feelings of guilt and inadequacy, loss of motivation and interest in life etc. Depression causes despair and devastation all over the world. The most popular mechanism of action that is thought to underlie depression is the monoamine theory which states that depression is caused by a deficit in noradrenaline and serotonin. Pharmacological evidence supports this theory as antidepressants aim to restore this deficit. SSRIs work by blocking the reuptake of serotonin hence more serotonin is available in the brain. However it is clear that there is more to depression than what we know today given that only 50% of patients respond to medication. We need more information and testing to gain a better understanding. Animal models are the way forward in this area. The Olfactory Bulbectomized rat is a good model as it only responds to chronic antidepressants and it exhibits behavioural changes – both of which humans do too. My project will look at the OB rat and how the levels of Tryptophan Hydroxylase, the rate-limiting enzyme in serotonin synthesis, plays a role. After the syndrome is established the levels of TPH will decrease, in theory this should lead to a reduction in serotonin. I want to investigate whether there is an optimal time for the decrease in TPH by measuring the levels in a time-related manner.
