Effect of Ketamine Treatment on Neuronal Oscillatory Activity in the Nucleus Accumbens and Hippocampus in an Animal Model of Treatment-Resistant Depression.
Depression is a globally prevalent disorder characterized by negative symptoms including amotivation and suicidality. Ketamine is a treatment that can provide rapid, long-lasting antidepressant effects, but also exhibits harsh psychomimetic side effects that greatly hinder its accessibility and tolerability. Macroscopic neuronal oscillations are essential for communication within the brain and are dysregulated in several neuropsychiatric disorders including depression. This study therefore used the Wistar-Kyoto (WKY) animal model of treatment resistant depression to examine the effects of ketamine on neural oscillatory activity in two brain regions implicated in the pathophysiology of depression, the nucleus accumbens (NAc) and hippocampus (HIP). At baseline, WKY males showed abnormalities in delta and theta power in the NAc and HIP, but not NAc-HIP coherence. Female WKY rats showed similar abnormalities in HIP, but not NAc, and increased NAc-HIP theta coherence. Ketamine administration normalized the dysfunction in NAc of males and theta coherence between NAc-HIP in females.