Differential Effects of Lorazepam on Sleep and Activity in C57BL/6J and BALB/cJ Strain Mice

摘要

Compared to C57BL/6 mice, BALB/c mice exhibit greater “anxiousness” on behavioral tests of anxiety, and can show significantly longer sleep disruptions after exposure to anxiogenic situations. Relative to C57BL/6 mice, BALB/c mice also have reduced benzodiazepine (BZ) receptor densities in the brain and fivefold less BZ receptor density in the amygdala, a region important in anxiety and in the control of arousal. Lorazepam is a BZ receptor full agonist and has been used to treat both anxiety and insomnia. Differences between C57BL/6 and BALB/c mice raise the question of whether BZ agonists would differentially impact sleep and activity in the two strains. We examined the effects of two dosages of lorazepam (0.5 mg/kg; 1.5 mg/kg) or saline alone (0.2 ml) on sleep and activity in C57BL/6 (n=8) and BALB/c (n=8) mice. Compared to saline, both dosages of lorazepam significant increased NREM and reduced activity in both strains. In C57BL/6 mice, REM was increased at both dosages. In BALB/c mice, the 0.5 mg/kg dosage had no significant influence on REM, whereas REM was significantly reduced after the 1.5 mg/kg dosage. The results demonstrate significant differences between C57BL/6 and BALB/c mice in the effects of lorazepam on REM, whereas the effects on NREM and activity were similar. Strain differences in the number BZ receptors in the amygdala, but not other brain regions, suggests possible site specificity in the effects of lorazepam on REM. These differences in BZ binding sites in the amygdala could be a significant factor in differences in the sleep response between C57 and BALB/c mice.