BDNF Alterations in Brain Areas and the Neurocircuitry Involved in the Antidepressant Effects of Ketamine in Animal Models, Suggest the Existence of a Primary Circuit of Depression
Journal of Integrative Neuroscience August 16, 2022 Ezio Carboni, Anna R. Carta 15 citations
Major depressive disorder is a leading cause of disability worldwide, and current treatments mostly target monoamine reuptake. The recent approval of esketamine as a rapid-acting antidepressant highlights glutamatergic transmission's role. This review examines the hippocampus, medial prefrontal cortex (mPFC), nucleus accumbens (NAc), lateral habenula (LHb), amygdala, and bed nucleus of stria terminalis (BNST) in animal models of depression. Chronic stress alters brain-derived neurotrophic factor (BDNF) expression and dendritic density in these areas. Ketamine and standard antidepressants can reverse these changes. The authors propose that the mPFC, NAc/ventral tegmental area (VTA), and hippocampus form a primary circuit where normal function supports resilience. Disruption by environmental challenges or activation of the amygdala, LHb, or BNST can spread detrimental effects and generate depression symptoms, including anhedonia.