Acute ketamine administration attenuates lipopolysaccharide-induced depressive-like behavior by reversing abnormal regional homogeneity in the nucleus accumbens.

Abstract

Ketamine has rapid antidepressant effects, but no study to date has investigated changes in resting-state brain activity following ketamine administration in inflammation-induced depression. The purpose of this study was to use blood oxygen level-dependent functional MRI to explore changes in the resting-state brain activity in a rat model of depression induced by lipopolysaccharide (LPS, 1 mg/kg) challenge and to examine whether acute ketamine administration can reverse LPS-induced depressive-like behavior. Here, we showed LPS-induced depressive-like behavior as evidenced by significantly reduced motility in the forced swim test. In addition, LPS-induced increases in plasma levels of proinflammatory cytokines were not completely reversed by acute ketamine administration, suggesting that ketamine exerts its antidepressant effects independently of a possible interference with LPS-induced inflammatory signaling. However, increased regional homogeneity (ReHo) was observed in some brain regions of LPS-exposed animals, including bilateral caudate putamen and nucleus accumbens, which were parts of the mood-regulating circuit. Moreover, ReHo values of bilateral caudate putamen and nucleus accumbens showed significant positive correlations with immobility time. Notably, the LPS-induced depressive-like behavior and increase of ReHo value in the right nucleus accumbens was reversed by acute ketamine administration. In summary, this study suggests that acute ketamine administration is capable of attenuating LPS-induced depressive-like behavior, at least partially by reversing abnormal ReHo in the right nucleus accumbens.