Investigation of the Role of Stimulation and Blockade of 5-HT7 Receptors in Ketamine Anesthesia.

Although several pieces of evidence have indicated the ability of the serotonin-7 receptor (5-HTR7) to modulate N-methyl-D-aspartate receptor (NMDAR) activation, the possible impact on ketamine anesthesia has not been examined directly. The purpose of the present study is thus to investigate the possible role of the 5-HTR7 in ketamine anesthesia using a 5-HTR7 agonist and/or antagonist. The influence of a 5-HTR7 agonist/antagonist on ketamine anesthesia for behavioral impact was assessed by testing potential anesthetic parameters. Its functional impact was assessed by mRNA expression with real-time PCR and immunostaining in the hippocampus and prefrontal cortex of mice. Two different doses of ketamine—high and low—were administered to induce anesthesia. In the high-dose ketamine-applied group in particular, the administration of both the 5-HTR7 agonist and antagonist intensified the anesthetic effect of ketamine. The reflection of the change in anesthesia parameters to 5-HTR7 expression was observed as an increase in the hippocampus and a decrease in the prefrontal cortex in the anesthetized groups by stimulation of 5-HTR7. It is noteworthy that the results of NMDAR expressions are parallel to the results of the 5-HTR7 expressions of both the hippocampus and the prefrontal cortex. The 5-HTR7 may play a role in ketamine anesthesia. It may act through NMDAR in ketamine anesthesia, depending on the parallelism between both receptors.