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Background and Objectives: A flavonoid kaempferol (KM) exerts an anti-inflammatory effect and is reportedly capable of preventing metabolic diseases. Nonetheless, a limited number of studies have been carried out on the antinociceptive effects of kaempferol.
Objectives: The present study aimed to investigate the involvement of serotonin receptors in the antinociceptive-like activity of KM in male Wistar rats using the tail-flick test.
Materials and Methods: The compounds (i.e., KM, morphine, and diclofenac) were intracerebroventricularly administered to rats for the examination of central effects on the thermal pain using the tail-flick test. For the evaluation of the involvement of serotonin receptors in the possible antinociceptive effects of kaempferol, several antagonists (i.e., tropisetron, ketanserin, GR113808, WAY 100635, and penbutolol) were used. Additionally, locomotor activity and motor responses were investigated by the rotarod test after KM treatment.
Results: The intracerebroventricular microinjections of KM showed antinociceptive effects using the tail-flick test. The pretreatment with tropisetron as a 5-HT₃ receptor antagonist at 1 and 10 mg completely reversed the KM-related antinociception. Furthermore, ketanserin (5-HT_2A receptor antagonist) and GR113808 (5-HT₄ receptor antagonist) both at 10 mg reduced KM-related antinociception; however, 5-HT_1A receptor antagonist WAY 100635 and 5-HT_1B antagonist penbutolol did not decrease KM-related antinociception. All KM doses were not observed with a significant effect on locomotor activity or motor reactions.
Conclusion: The results of the current study suggested that serotonergic receptors (i.e., 5-HT_2A, 5-HT₃, and 5-HT₄) are effective in the KM antinociceptive activity in male rats.

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Background and Objectives: Kaempferol (KM) is one of the most important plants with neuroprotection and analgesic effects. In addition, bicuculline (BIC) is a competitive antagonist of the GABA_A ionotropic receptor (the most important targets of benzodiazepines and other anxiety suppressants). In this study, intracerebroventricular microinjection of KM on anxiety and its interaction with GABAergic mechanism were investigated in male rats.
Materials and Methods: In this exploratory investigation, the male rats were divided into the following groups: control (saline), groups treated by KM (0.5 and 2 mg/rat), DMSO (1mg/rat), KM 0.5+BIC1 mg/rat, KM 0.5+BIC4 mg/rat, KM 2+BIC1 mg/rat, BIC groups (1, 4 mg/rat), and KM 2+BIC 4 mg/rat. Besides, an elevated plus-maze paradigm was used for the evaluation of the anxiety.
 
Results: Statistical analysis revealed that the indices of TTOA in KM groups (0.5 and 2 mg/rat) significantly increased in comparison to the control group (P<0.05 and P<0.01, respectively). Moreover, regarding the involvement of the GABAergic system in the anxiolytic-like activity of KM, it was demonstrated that the TTOA related to co-administration of KM (0.5mg/rat) with bicuculline (1mg/rat) significantly reduced, compared to the control group (P<0.05).
 
Conclusion: According to the obtained results, the use of KM can likely improve anxiety through GABAergic mechanism(s).