Drug withdrawal-induced depression: serotonergic and plasticity changes in animal models

This review discusses recent research of mood disorders associated with the cessation of psychoactive substances, with an emphasis on preclinical studies that have been published in the last decade. Animal models exhibiting anhedonic and depressive-like behaviours associated with drug withdrawal have been used to study the neurobiology of mood disorders and have culminated in the identification of novel targets for the treatment of depressive-like symptoms. This review will introduce the behavioural as well as the neurochemical and plasticity changes in depressed patients and several animal models of depression. Following, we provide a more in-depth discussion of the role of serotonergic neurotransmission and Hypothalamic-Pituitary-Adrenal (HPA) axis regulation as well as the neurogenic changes occurring after chronic drug intake focusing on the withdrawal associated depression. Although we mainly focus on animal data, some relevant human studies are also discussed. Establishing the commonalities of depression and drug-seeking behaviour will allow us to elucidate the factors driving the high co-morbidity between mood disorders and drug dependence.