Differential effects of lorazepam on sleep and activity in C57BL/6J and BALB/cJ strain mice.
Compared to C57BL/6 mice, BALB/c mice exhibit greater 'anxiousness' on behavioural 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 impact sleep and activity differentially in the two strains. We examined the effects of two doses of lorazepam (0.5 and 1.5 mg kg(-1)) or saline alone (0.2 mL) on sleep and activity in C57BL/6 (n = 8) and BALB/c (n = 7) mice. Compared to saline, both doses of lorazepam significantly increased non-rapid eye movement (NREM) and reduced activity in both strains. In C57BL/6 mice, rapid eye movement (REM) was increased at both doses. In BALB/c mice, the 0.5 mg kg(-1) dose had no significant influence on REM, whereas REM was reduced significantly after the 1.5 mg kg(-1) dose. 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 of 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.
Tang
Xiangdong
X
Department of Psychiatry, Sleep Medicine Center, Psychiatric Laboratory and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China. xiangdong.tang@gmail.com
Yang
Linghui
L
Fishback
Nancy F
NF
Sanford
Larry D
LD
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011963:Receptors, GABA-A / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D013045:Species Specificity
D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D008140:Lorazepam
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