![Deletion of HCN1 channels from forebrain reduced sensitivity of mice to hypnotic actions of ketamine. (A and B) Mice were injected with incrementing concentrations of ketamine (5–20 mg/kg, IV), and the fraction of HCN1f/f and CaMKCre:HCN1f/f mice that failed to right themselves (loss-of-righting reflex [LORR]) was determined as a measure of hypnosis. CaMKCre:HCN1f/f mice were less sensitive to hypnotic effects of ketamine, as indicated by increased EC50 for ketamine-induced LORR (A: F1,328 = 33.2, P < 0.0001 by ANOVA) and reduced duration of the LORR (B: F1,211 = 10.4, P < 0.002 by two-way ANOVA). (C) The latency for mice to remove their tail from a radiant heat source was essentially identical in HCN1f/f and CaMKCre:HCN1f/f mice under control conditions, and ketamine (20 mg/kg, IV) evoked a similar transient increase in latency in both sets of mice. (D) The duration that HCN1f/f and CaMKCre:HCN1f/f mice were able to stay on an accelerating RotaRod (Med Associates Inc., Georgia, VT) was not different before or immediately after treatment with a subanesthetic dose of ketamine (2.5 mg/kg, IV) (n = 31 and 52, P < 0.05, * HCN1f/f:cre vs. HCN1f/f).](https://asa2.silverchair-cdn.com/asa2/content_public/journal/anesthesiology/118/4/10.1097_aln.0b013e318287b7c8/2/13ff05.png?Expires=1717034223&Signature=WDEmmEmuH6JxyHuyHobD94zlxQS~4-L8I0QmEtVxze5q4lb3eiqyzKdoqJyHTBtWCAQi0xJRpGd8J5O~QTbH0fliZ32tbnvD8KObemWsMG2FmJ3CkEpaNg3O0AILn2b3tOkqALkIHgxG3m4TIrrxhKKHla4weJoFUT8LUCI9GxfmVYnH1Zrtau2-GqtCdWTqmhmiA7L~0D57L-bvSbk8HTEAc8cZNCTMMPH-fKwiUT31xHlmkRn0DETISNR7l84dTOZv7TzDi3Gtl~PJrxSiujaMVPEeQgG9BTTNVNQPs8sXe9x1uHebasYeTutFU25lOPm8d93O44-hLlzprRc5TQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Deletion of HCN1 channels from forebrain reduced sensitivity of mice to hypnotic actions of ketamine. (A and B) Mice were injected with incrementing concentrations of ketamine (5–20 mg/kg, IV), and the fraction of HCN1f/f and CaMKCre:HCN1f/f mice that failed to right themselves (loss-of-righting reflex [LORR]) was determined as a measure of hypnosis. CaMKCre:HCN1f/f mice were less sensitive to hypnotic effects of ketamine, as indicated by increased EC50 for ketamine-induced LORR (A: F1,328 = 33.2, P < 0.0001 by ANOVA) and reduced duration of the LORR (B: F1,211 = 10.4, P < 0.002 by two-way ANOVA). (C) The latency for mice to remove their tail from a radiant heat source was essentially identical in HCN1f/f and CaMKCre:HCN1f/f mice under control conditions, and ketamine (20 mg/kg, IV) evoked a similar transient increase in latency in both sets of mice. (D) The duration that HCN1f/f and CaMKCre:HCN1f/f mice were able to stay on an accelerating RotaRod (Med Associates Inc., Georgia, VT) was not different before or immediately after treatment with a subanesthetic dose of ketamine (2.5 mg/kg, IV) (n = 31 and 52, P < 0.05, * HCN1f/f:cre vs. HCN1f/f).
