Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2022.922750 · Published: August 22, 2022

Simple Explanation

This study investigates how tandospirone, a drug used for anxiety, can help with gut problems caused by stress. Researchers used rats that were stressed to mimic irritable bowel syndrome symptoms. The study discovered that stressed rats had more serotonin, fewer receptors for serotonin (5-HT1A), and more brain activity (theta oscillations) in a specific brain area (ACC). Tandospirone helped reduce anxiety and gut sensitivity in these rats by targeting serotonin receptors and calming the brain activity in the ACC.

Study Duration

10 consecutive days

Participants

Adult male Wistar rats (200–250 g)

Evidence Level

Not specified

Key Findings

1
Tandospirone (TDS) ameliorated visceral hypersensitivity and anxiety-like behavior induced by water avoidance stress.
2
Stress increased 5-HT concentration, reduced 5-HT1AR expression, and enhanced theta band power in anterior cingulate cortex.
3
The effects of TDS in stress-induced visceral hypersensitivity were mediated by 5-HT1ARs.

Research Summary

This study found that stress-induced visceral hypersensitivity is linked to downregulated 5-HT1ARs, which in turn enhances ACC theta oscillations. Tandospirone (TDS) was found to alleviate both visceral hypersensitivity and anxiety-like behavior caused by stress. The therapeutic effects of TDS are likely due to its activation of 5-HT1A receptors in the ACC, which inhibits the enhancement of theta oscillations. These findings reveal a novel mechanism in the 5-HT1AR–theta-oscillation pathway, offering a potential explanation for how TDS can relieve anxiety and visceral pain.

Practical Implications

IBS Treatment Enhancement

The combinative use of tandospirone with other medicines for patients with IBS with anxiety may enhance therapeutic outcomes.

Visceral Pain Management

The identified mechanism may be of general importance for other visceral pain, such as pelvic pain or vulvodynia.

Novel Therapeutic Targets

The study provides evidence for a novel mechanism of regulating the 5-HT1AR–theta-oscillation pathway, which can be targeted to relieve anxiety and visceral pain.

Study Limitations

1
The study was conducted only on male rats, limiting the generalization of this observation to female subjects.
2
The level of anxiety of sham-WAS (same treatment as WAS but in the tank without water) rats varied between individuals due to diﬀerent stressful responses of rats to the elevated vertical platform
3
There was a period of time without TDS administration between stress and visceral sensitivity measurement which may have reduced the eﬀect of TDS

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