The stressed brain : Inquiry into neurobiological changes associated with stress, depression and novel antidepressant treatment

Do you recognize the symptoms of stress – tensing up, hyperventilating, rapid heart beating? These are our body’s reactions to events of danger – whether it is real or imagined. Stress can save your life and boost your productivity, but if you cannot cope with it, severe and continuous stress may harm you. Stress and its related disorders pose a considerable threat to health in modern societies. Stressful life events promote changes in the brain that may lead to psychopathology, such as major depression. Although various remedies have been developed to treat depressive disorder, their therapeutic effects are suboptimal and the specific mechanisms of action remain obscure. This PhD thesis entitled “The Stressed Brain” aims to dissect fundamental stress-induced alterations in the brain that might predispose to psychopathology. Moreover, it investigates neurobiological changes associated with treatment of agomelatine, a new antidepressant with an innovative pharmacological profile (agomelatine acts as a melatonin receptor agonist and serotonergic 5-HT2C receptor antagonist). The experimental work presented in this thesis reveals that chronic stress is accompanied by neuronal and synaptic changes in the brain. Nonetheless, the stress effects have specific temporal dynamics and depend on the type and duration of the stress experience. The current thesis also suggests that processes of neuronal and synaptic plasticity are involved in the action mechanism of agomelatine. This information yields more general insight into mechanisms underlying the recovery from stress-related psychopathologies, and thereby may open up novel prospects for their treatment and prevention.