Introduction

The present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats.

Methods

Pregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively.

Results

The results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats.

Conclusion

It can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.

中文翻译：

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白藜芦醇对 VPA 诱导的自闭症样大鼠社会行为和伤害性反应的性别依赖性改变。

简介

本研究旨在阐明白藜芦醇 (RSV) 对雌性和雄性大鼠丙戊酸 (VPA) 诱导的自闭症样模型中社会行为改变和伤害性反应的影响。

方法

怀孕的Wistar大鼠随机分为五组。动物接受盐水、DMSO、VPA、RSV 和 RSV + VPA。在胚胎第 12.5 天 (E12.5) 施用 VPA (600 mg/kg, ip) 并在 E6.5 上施用白藜芦醇 (3.6 mg/kg, sc) 预处理直至 E18.5。所有后代在出生后第 21 天断奶，并在第 60 天在雄性和雌性大鼠中进行实验。分别进行社交互动、热板和甩尾测试以评估社交缺陷和痛阈。分别计算社交指数（SI）、社交新奇指数（SNI）和潜伏时间作为社交行为和痛阈的标准指标。

结果

结果表明，系统性腹腔注射 VPA (600 mg/kg) 显着降低社会互动试验 (SIT) 中的 SI 和 SNI，尤其是雄性大鼠，表明 VPA 引起的社会障碍。RSV (3.6 mg/kg, sc) 在雄性大鼠中逆转了 VPA 诱导的社交缺陷，但在雌性组中则不然。VPA 给药导致雄性大鼠热板和甩尾试验中的潜伏时间显着增加，而对雌性大鼠则没有这种显着影响。在雄性大鼠中，与丙戊酸组相比，RSV 与 VPA 联合给药对潜伏时间没有显着影响。值得注意的是，RSV 本身对雌性和雄性大鼠的 SI、SNI 和潜伏时间没有显着影响。

结论

可以得出结论，丙戊酸会产生类似自闭症的行为并增加雄性大鼠的疼痛阈值，这可以通过施用白藜芦醇至少部分改善。需要进一步的研究来阐明丙戊酸和白藜芦醇诱导作用的分子机制。