Increasing evidence shows the close relationship between hippocampal glutamatergic and serotonergic systems through the modulation of behavioral responses. This study aimed to investigate the possible involvement of 5-HT₄ receptors in the CA3 hippocampal region in anxiolytic-like effects induced by D-AP5 (a competitive antagonist of the glutamate NMDA [N-Methyl-D-aspartate] receptor). Male Wistar rats were placed in the elevated plus maze (EPM) apparatus that is used to assess anxiety-related behaviors, and the percentages of open arm time (%OAT) and open arm entries (%OAE) which are associated with anxiety-related behaviors were measured. The close arm entries (CAE) which is correlated with locomotor activity was also evaluated. The results showed that, intra-CA3 injection of D-AP5 (0.4 μg/rat), RS67333 (1.2 μg/rat; a 5-HT₄ receptor agonist), and RS23597-190 (1.2 μg/rat; a 5-HT₄ receptor antagonist) increased %OAT and %OAE, indicating the anxiolytic-like effect of these drugs. Also, only RS23597-190 (1.2 μg/rat) decreased CAE. Intra-CA3 injection of sub-threshold dose of RS67333 (0.012 μg/rat) or RS23597-190 (0.012 μg/rat), 5 min before the injection of D-AP5 (0.2 μg/rat) increased %OAT, indicating potentiating the anxiolytic-like effect of D-AP5. The isobolographic analyses also showed the additive or synergistic anxiolytic-like effect of intra-CA3 co-administration of D-AP5 with RS67333 or RS23597-190, respectively. In conclusion, CA3 5-HT₄ receptors are involved in D-AP5-induced anxiolytic-like behaviors in rats.

越来越多的证据表明，海马谷氨酸能和血清素能系统通过行为反应的调节存在密切关系。本研究旨在调查CA3 海马区的 5-HT ₄受体可能参与D-AP5（一种谷氨酸 NMDA 的竞争性拮抗剂 [ N-甲基-D-天冬氨酸]受体）。将雄性 Wistar 大鼠置于高架十字迷宫 (EPM) 装置中，用于评估焦虑相关行为，以及与焦虑相关的开放臂时间 (%OAT) 和开放臂进入 (%OAE) 的百分比行为进行了测量。还评估了与运动活动相关的近臂进入（CAE）。结果表明，CA3内注射D-AP5（0.4μg/大鼠）、RS67333（1.2μg/大鼠；5-HT ₄受体激动剂）和RS23597-190（1.2μg/大鼠；5-HT ₄受体拮抗剂）增加了 %OAT 和 %OAE，表明这些药物具有抗焦虑样作用。此外，只有 RS23597-190 (1.2 μg/rat) 降低了 CAE。在注射 D-AP5 (0.2 μg/大鼠) 前 5 分钟，CA3 内注射亚阈值剂量的 RS67333 (0.012 μg/大鼠) 或 RS23597-190 (0.012 μg/大鼠) 增加了 %OAT，表明增强了D-AP5 的抗焦虑样作用。等值线图分析还显示了 D-AP5 与 RS67333 或 RS23597-190 分别在 CA3 内共同给药的累加或协同抗焦虑样作用。总之，CA3 5-HT ₄受体与D-AP5诱导的大鼠抗焦虑样行为有关。