The effect of low and high concentrations of halothane, enflurane, and isoflurane on posttraining memory function was studied in male ddN mice. Mice were trained to escape an aversive electric foot shock as an unconditioned stimulus within 3 s after being exposed to light and a buzzer as a conditioned stimulus. Immediately after training (first session: 30 trials), the animals were exposed to halothane, enflurane, or isoflurane for 120 min and then were tested again on the avoidance task (second session: 30 trials) 22 h after cessation of exposure. The performance ratios, [B/A] (i.e., A is the score in the first session, and B the score in the second) were compared between the anesthetized groups and their respective control (nonanesthetized) groups. Mean performance ratios in the control groups ([B/A]c) ranged from 136.8% to 163.9% and those in the anesthetized groups ([B/A]a) ranged from 151.4% to 174.7%. [B/A] in each anesthetized group exceeded [B/A] in its corresponding control group. [B/A]a significantly exceeded [B/A]c by 13.1% in the 1.23 minimum alveolar concentration (MAC) enflurane group (P < 0.05) and by 12.4% in the 0.29 MAC isoflurane group (P < 0.05). These results suggest that posttraining exposure to volatile anesthetics facilitates memory.
Background Previously the authors found that a single post-training exposure to enflurane or isoflurane, but not halothane, enhanced memory storage in an active avoidance task, which is a behavior with underlying mechanisms that are poorly understood and still debated. In contrast, spatial tasks are known to depend on hippocampal functions. This study investigated the effects of repetitive post-training exposure to enflurane on spatial memory in mice. Methods Using an eight-arm radial maze, 80 mice were trained to eat a pellet placed on the end of each of the eight arms. Training occurred on four consecutive days with one trial per day. The number of errors in the first eight choices was recorded to determine performances for each day of training. Immediately after each training session, mice in the enflurane group received 1 h exposure to 0.5%, 1%, or 2% enflurane in air through a calibrated vaporizer. The performance ratios (the ratio of errors on each day compared with the first day of the 4 days) in the control and the enflurane groups were compared. Results The performance ratios (which equals the mean of the error in the fourth day/the error in the first day) in the control, and 0.5%, 1%, and 2% enflurane groups were 0.66, 0.65, and 0.32 (P < 0.01, vs. control), and 0.46 (P < 0.05, vs. control), respectively. Conclusions Repetitive post-training exposure to 1% and 2% enflurane significantly enhanced spatial memory in the eight-arm radial maze task. Enflurane enhances consolidation of spatial memory, possibly by affecting hippocampal activity.
Using loss of the righting reflex, we determined the ED50 values for enflurane, isoflurane, sevoflurane and halothane in white-haired ddN mice and black-haired C57BL mice. The ED50s (Mean +/- SEM) in ddN and C57BL mice for enflurane were 1.65 +/- 0.01 and 1.19 +/- 0.01% atm, for isoflurane 1.02 +/- 0.01 and 0.74 +/- 0.01% atm, for sevoflurane 2.29 +/- 0.03 and 1.95 +/- 0.03% atm, and for halothane 0.97 +/- 0.01 and 0.97 +/- 0.01% atm, respectively. The results indicate that the ddN strain is more resistant to enflurane, isoflurane and sevoflurane than the C57BL strain. The sensitivities to enflurane and isoflurane is F1 progeny of reciprocal crosses between ddN and C57BL mice revealed that in the ddN strain enflurane resistance is an incompletely dominant or polygenic character, isoflurane resistance in ddN strain is an autosomal recessive character and both are controlled by genes on the sex (X) chromosome. Enflurane and isoflurane resistances are controlled by at least 2 genes, one on the X chromosome, and each resistance is controlled by a different genetic mode
We performed a classic backcross analysis to examine the basic genetic nature of enflurane (ENF) and isoflurane (ISO) anesthetic requirement in two inbred mice strains, C57BL (BL) and ddN. We have previously reported different ENF and ISO anesthetic requirements in these two strains. BL (n = 22) and ddN (n = 26) mice were used as parents and were reciprocally crossed to produce F1 hybrid mice. Each F1 offspring was crossed to its parent to produce backcross siblings (BF1). Anesthetic end point was determined as the loss of righting reflex. Measurement of anesthetic requirement was performed during 8-12 wk after birth. Although ddN mice showed slightly less resistance to ENF and ISO compared with our previous report, they were more resistant than BL mice. Multivariate regression analysis of parents' and F1 hybrids' data revealed that, while maternal factors and factors on autosomes were related to both anesthetics, the factors on the X chromosome were ENF specific. A wide variation in anesthetic requirements among BF1 progeny suggested multifactorial inheritance. The regression equations obtained did not always predict anesthetic requirement in BF1 progeny. These discrepancies may be due to the epistatic interaction of related genes. We conclude that multiple but different genetic factors are involved in determining ENF and ISO anesthetic requirements in BL and ddN mice.
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