T175. Exploring the Synaptic Basis of Rapid Antidepressant Treatments in a Congenital Learned Helplessness Model

Abstract

Depression leads to significant impairment in daily function. The prolonged time course necessary for current pharmacological treatment may extend suffering, and increase risk of suicide. Therefore, development of rapid treatments may be helpful by speeding recovery time and reducing suicidality. Two treatments with reproducible clinical efficacy are total sleep deprivation and ketamine administration. Amazingly, these treatments not only alleviate depressive symptoms in refractory patients, but also rapidly reduce suicidality. We used an inbred line of congenital learned helplessness (cLH) rats, a validated model of Major Depressive Disorder (MDD), to examine the synaptic effects of both sleep deprivation and ketamine administration. These rats have a hyperactive lateral habenula (LHb), an epithalamic nucleus that regulates dopamine release from the VTA. Hyperactivity in the habenula leads to decreased dopamine release from the VTA, and depression-like symptoms in these rodents.