Venlafaxine and synbiotic attenuated learned fearlike behavior and recognition memory impairment in immobilized-stressed rats

Stress disturbs the gut-brain axis and contributes to the development of mood disorders and memory impairment. Recent findings on the anti-stress effects of monoamine modulators have shown that the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine (Vlx) is more effective in stressed rodents. However, the effects of Vlx on microbiota and memory impairment- and stress-related behaviors are still unknown. Synbiotics (Syn), a mixture of probiotics and prebiotics, can modify the gut microbiome; however, the effects of anti-anxiety and anti-memory deficits are still not well understood. Therefore, this study proposed to compare the effectiveness of Vlx and Syn in the reduction of learned fearand memory impairment-like behaviors in an animal model of stress.

Forty male adult Wistar rats were subjected to stress by immobilization in a restrainer for 2h per day and were administered 10mg/kg Vlx and/or 2g of Syn containing 1.01010 CFU probiotic strains and prebiotic oligosaccharides daily for 14 days. Learned fear, recognition memory and locomotor activity were evaluated by the elevated-T maze, novel objective recognition and open field tests. Blood samples and adrenal glands were collected to measure the circulating corticosterone levels and relative adrenal weights, which were used as markers of stress responses.

The immobilized-stressed rats showed hyperactivity in stress responses, as demonstrated by increased relative adrenal weights and serum corticosterone levels. Both Vlx and Syn reduced the increase in serum corticosterone levels in stressed rats. Furthermore, Vlx- and/or Syn-treated stressed rats had fewer learned fear-like behaviors and a higher discrimination index without any locomotor activity changes than vehicle-treated stressed rats.

Syn supplementation had comparable effects to SNRIs in alleviating the risk of developing anxiety disorders and memory impairment in stressed individuals or psychiatric patients.