Genistein Prevents Single Prolonged Stress-Induced Cognitive Impairment in a Post-Traumatic Stress Disorder Rat Model via Activation of the Serotonergic System.

Post-traumatic stress disorder (PTSD) is a stress-associated mental disorder characterized by an imbalance of neurotransmitters in response to traumatic events or fear. Genistein (GEN), a natural isoflavone, has been shown to exhibit neuroprotective effects. Here, we used the Morris water maze (MWM) and object recognition task (ORT) tests to examine the effects of GEN on cognitive impairment in rats after exposure to single prolonged stress (SPS), and its interaction with the serotonergic system. After exposure to SPS, male rats received GEN (2, 4, and 10 mg/kg, i.p.) for 14 days. Daily GEN administration significantly improved cognitive function in the ORT and MWM tests. GEN treatment also inhibited SPS-induced decreases in serotonin (5-HT) levels in the medial prefrontal cortex and hippocampus. These increased 5-HT concentrations in response to GEN treatment could be partially attributed to the ratio of 5-hydroxyindoleacetic acid/5-HT in the hippocampus. Our findings suggest that GEN significantly attenuates SPS-induced memory deficits in rats and may represent an effective therapeutic option for the treatment of PTSD.