TY - JOUR
T1 - A novel method to assess initial sensitivity and acute functional tolerance to hypnotic effects of ethanol
AU - Ponomarev, Igor
AU - Crabbe, John C.
PY - 2002
Y1 - 2002
N2 - Loss of righting reflex (LRR) has traditionally been used to estimate hypnotic sensitivity to ethanol in rodents. Traditional methods of monitoring ethanol-induced sedation seems to lack accuracy in estimating blood ethanol concentration (BEC) at initial LRR, a measure of initial sensitivity. Herein, we present a novel method that improves detection of the onset of LRR by using a new apparatus and a loss-of-function criterion of 5 s. DBA/2J and C57BL/6J mice were placed in cylindrical restrainers after injection of 3 g/kg (20% v/v) ethanol. Restrainers were then turned until mice were no longer able to right themselves within 5 s from a position on their back, which represented the endpoint of the initial loss of righting reflex. Initial sensitivity and acute functional tolerance (AFT) to ethanol were assessed in the same group of mice by quantifying BEC at the initial loss and subsequent recoveries of righting reflex over four sequential injections [3 g/kg + (3 x 0.5 g/kg)]. Initial brain sensitivity was calculated from BEC at the first LRR, using the parameters of ethanol uptake kinetics. These values of initial sensitivity were similar for the two strains. On the other hand, DBA/2J mice recovered at higher BEC than C57BL/6J animals. AFT calculated as a difference between the maximum BEC at any recovery and the value of initial sensitivity was greater in DBA/2J mice. These results show that the novel method is a sensitive tool for the measurement of initial sensitivity and detection of AFT to the hypnotic effects of ethanol.
AB - Loss of righting reflex (LRR) has traditionally been used to estimate hypnotic sensitivity to ethanol in rodents. Traditional methods of monitoring ethanol-induced sedation seems to lack accuracy in estimating blood ethanol concentration (BEC) at initial LRR, a measure of initial sensitivity. Herein, we present a novel method that improves detection of the onset of LRR by using a new apparatus and a loss-of-function criterion of 5 s. DBA/2J and C57BL/6J mice were placed in cylindrical restrainers after injection of 3 g/kg (20% v/v) ethanol. Restrainers were then turned until mice were no longer able to right themselves within 5 s from a position on their back, which represented the endpoint of the initial loss of righting reflex. Initial sensitivity and acute functional tolerance (AFT) to ethanol were assessed in the same group of mice by quantifying BEC at the initial loss and subsequent recoveries of righting reflex over four sequential injections [3 g/kg + (3 x 0.5 g/kg)]. Initial brain sensitivity was calculated from BEC at the first LRR, using the parameters of ethanol uptake kinetics. These values of initial sensitivity were similar for the two strains. On the other hand, DBA/2J mice recovered at higher BEC than C57BL/6J animals. AFT calculated as a difference between the maximum BEC at any recovery and the value of initial sensitivity was greater in DBA/2J mice. These results show that the novel method is a sensitive tool for the measurement of initial sensitivity and detection of AFT to the hypnotic effects of ethanol.
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U2 - 10.1124/jpet.302.1.257
DO - 10.1124/jpet.302.1.257
M3 - Article
C2 - 12065725
AN - SCOPUS:0036082359
SN - 0022-3565
VL - 302
SP - 257
EP - 263
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -