Mapping functional changes in rat brain in response to altered serotonergic function using BOLD fMRI

Introduction Dysfunction in the brain serotonergic (5-HT) system is thought to underlie human depression. Selective Serotonin Re-uptake Inhibitors (SSRIs) are widely used antidepressant drugs whose therapeutic onset are delayed for several weeks whilst neuroadaptive changes take place in the brain, after which the previously disturbed serotonergic neurotransmission is restored. A suggested way of hastening the action of SSRIs is to combine them with 5-HT receptor antagonists. This effect has been shown with 5HT1A autoreceptor antagonists in rats, but was more variable in the clinic . 5HT2C receptor antagonists may also accelerate the therapeutic onset of SSRIs and the mechanisms involved are under investigation .