Sato Y. , Kobayashi E. , Hakamata Y. , Kobahashi M. , Wainai T

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Chronopharmacological studies of ketamine in normal and NMDA Ε1 receptor knockout mice† Sato Y. , Kobayashi E. , Hakamata Y. , Kobahashi M. , Wainai T. , Murayama T. , Mishina M. , Seo N. British Journal of Anaesthesia Volume 92, Issue 6, Pages 859-864 (June 2004) DOI: 10.1093/bja/aeh144 Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

Fig 1 Daily variation in water intake in wild‐type and NMDA receptor Ε1 subunit KO mice. Water intake was measured every 6 h (01:00–07:00, 07:00–013:00, 13:00–19:00, and 19:00–01:00) with average water intake during each interval were obtained in wild‐type and KO mice. Water consumptions showed similar circadian patterns in both wild‐type and NMDA receptor Ε1 subunit KO mice, implying a daily locomotor rhythm in these mice. Error bar, sd (n=6 in each group). British Journal of Anaesthesia 2004 92, 859-864DOI: (10.1093/bja/aeh144) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

Fig 2 Daily variation in the effect of ketamine on LORR in wild‐type mice. Ketamine (200 mg·kg–1) was administered intraperitoneally at 04:00, 10:00, 16:00, and 22:00. The duration of LORR was measured as the sleep time. Daily variation in the effect of ketamine exhibited a statistically significant circadian rhythm (P<0.001) and comparison of the duration of LORR at 10:00 and 22:00 showed a significant difference (P=0.001). Error bar, sd (n=12 in each group). British Journal of Anaesthesia 2004 92, 859-864DOI: (10.1093/bja/aeh144) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

Fig 3 Mean plasma concentrations of ketamine in wild‐type mice after drug administration at 10:00 or 22:00. No significant difference was observed between the two groups. Error bar, sd (n=8 in each group). British Journal of Anaesthesia 2004 92, 859-864DOI: (10.1093/bja/aeh144) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

Fig 4 Evaluation of the hypnotic effects of ketamine in wild‐type mice and in the NMDA receptor Ε1 subunit KO mice. Ketamine (200 mg·kg–1) was administered intraperitoneally at 10:00 and 22:00. The duration of LORR was measured as the sleep time. Mean sleep time was significantly shorter in the NMDA receptor Ε1 subunit KO mice than in the wild‐type mice at 22:00 (P<0.001), but no significant difference was observed at 10:00. Whilst a significant dosing time dependency was observed in wild‐type mice (P=0.001) a significant difference in the hypnotic effect was not found between the two injection times in KO mice. Error bar, sd (n=12 in each group). British Journal of Anaesthesia 2004 92, 859-864DOI: (10.1093/bja/aeh144) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions