OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neur...OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.展开更多
The quantitative anaesthesia assessment technique was used to evaluate the effectiveness of ketamine, ketamine-xylidinothiazoline in rhesus monkey. Total 20 healthy adult rhesus monkeys were divided into two groups an...The quantitative anaesthesia assessment technique was used to evaluate the effectiveness of ketamine, ketamine-xylidinothiazoline in rhesus monkey. Total 20 healthy adult rhesus monkeys were divided into two groups and anaesthetized using either intramuscular （IM） ketamine （20 mg·kg^-1） or ketamine （5 mg·kg^-1 IM） and xylidinothiazoline （1 mg·kg^-1 IM）. During anaesthesia rectal temperature, respiratory rate, heart rate, saturation of blood oxygen and blood pressure were recorded. The degree of sedation, analgesia, muscle relaxation were monitored either. The results showed that ketamine alone did not produce adequate anaesthesia, and the combination of xylidinothiazoline and ketamine provided adequate anesthesia for rhesus monkeys with no significant side effects and little effects on respiration and circulation.展开更多
文摘OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.
文摘The quantitative anaesthesia assessment technique was used to evaluate the effectiveness of ketamine, ketamine-xylidinothiazoline in rhesus monkey. Total 20 healthy adult rhesus monkeys were divided into two groups and anaesthetized using either intramuscular （IM） ketamine （20 mg·kg^-1） or ketamine （5 mg·kg^-1 IM） and xylidinothiazoline （1 mg·kg^-1 IM）. During anaesthesia rectal temperature, respiratory rate, heart rate, saturation of blood oxygen and blood pressure were recorded. The degree of sedation, analgesia, muscle relaxation were monitored either. The results showed that ketamine alone did not produce adequate anaesthesia, and the combination of xylidinothiazoline and ketamine provided adequate anesthesia for rhesus monkeys with no significant side effects and little effects on respiration and circulation.
