title: Differential effects of lorazepam on sleep and activity in C57BL/6J and BALB/cJ strain mice.
abstract: 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.
authors.affiliation: 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
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Tang
authors.forename: Linghui
authors.initials: L
authors.lastname: Yang
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Fishback
authors.forename: Larry D
authors.initials: LD
authors.lastname: Sanford
mesh_terms: 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
chemical_list: D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D008140:Lorazepam
references.citation: Eur J Pharmacol. 1992 Aug 6;218(2-3):283-6
references.pmid: 1330599
references.citation: Sleep. 2003 Aug 1;26(5):527-40
references.pmid: 12938805
references.citation: Life Sci. 1992;50(15):1117-28
references.pmid: 1556906
references.citation: Mol Psychiatry. 2001 Jan;6(1):13-34
references.pmid: 11244481
references.citation: Psychopharmacology (Berl). 2000 Feb;148(2):164-70
references.pmid: 10663431
references.citation: Neuropsychopharmacology. 2004 Jul;29(7):1344-52
references.pmid: 15085086
references.citation: Psychopharmacology (Berl). 1991;103(4):473-9
references.pmid: 1676527
references.citation: Pharmacol Biochem Behav. 2000 Jan 1;65(1):35-8
references.pmid: 10638633
references.citation: Arch Ital Biol. 1995 Dec;134(1):81-99
references.pmid: 8919194
references.citation: Annu Rev Neurosci. 1992;15:353-75
references.pmid: 1575447
references.citation: Arch Gen Psychiatry. 2005 Mar;62(3):282-8
references.pmid: 15753241
references.citation: Behav Brain Res. 2001 Nov 1;125(1-2):141-9
references.pmid: 11682105
references.citation: Sleep Res Online. 1998;1(3):109-13
references.pmid: 11382866
references.citation: Trends Neurosci. 1994 May;17(5):208-14
references.pmid: 7520203
references.citation: J Gerontol. 1975 May;30(3):257-63
references.pmid: 1120887
references.citation: Am J Psychiatry. 2007 Feb;164(2):318-27
references.pmid: 17267796
references.citation: J Neurosci. 1983 Oct;3(10):2091-7
references.pmid: 6311996
references.citation: Brain Res. 1999 Jul 17;835(1):18-26
references.pmid: 10448192
references.citation: Brain Res. 2002 Nov 29;956(2):276-84
references.pmid: 12445696
references.citation: Neuroreport. 1996 Jan 31;7(2):577-80
references.pmid: 8730833
references.citation: Behav Brain Res. 2004 Sep 23;154(1):137-47
references.pmid: 15302119
references.citation: Neuroscience. 1988 Jun;25(3):771-95
references.pmid: 2841624
references.citation: Neuroreport. 1996 Dec 20;8(1):117-22
references.pmid: 9051764
references.citation: J Clin Psychiatry. 2004;65 Suppl 5:7-12
references.pmid: 15078112
references.citation: Eur J Pharmacol. 1979 Jun;56(1-2):163-6
references.pmid: 572777
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1984;8(1):19-31
references.pmid: 6145185
references.citation: Int Clin Psychopharmacol. 1999 Mar;14(2):81-9
references.pmid: 10220122
references.citation: Sheng Li Xue Bao. 1998 Dec;50(6):688-92
references.pmid: 11367683
references.citation: Behav Brain Res. 2007 Aug 6;181(2):180-90
references.pmid: 17517441
references.citation: Sleep. 2002 Sep 15;25(6):691-9
references.pmid: 12224849
references.citation: Brain Res. 1995 Feb 13;671(2):213-21
references.pmid: 7743210
references.citation: Biol Psychiatry. 1995 Apr 1;37(7):473-6
references.pmid: 7786962
references.citation: Physiol Behav. 2005 Jul 21;85(4):419-29
references.pmid: 16019041
references.citation: Psychopharmacology (Berl). 1997 Jul;132(2):107-24
references.pmid: 9266608
references.citation: Neuropsychopharmacology. 1993 May;8(3):227-32
references.pmid: 8507350
references.citation: Behav Brain Res. 2002 Nov 15;136(2):555-69
references.pmid: 12429418
references.citation: Behav Genet. 2003 Jan;33(1):43-58
references.pmid: 12645821
references.citation: Behav Genet. 1994 Mar;24(2):171-80
references.pmid: 8024534
references.citation: Pharmacol Ther. 1990;47(2):147-65
references.pmid: 2203068
references.citation: Psychopharmacology (Berl). 1989;98(1):38-44
references.pmid: 2567034
references.citation: Brain Res. 1991 Jul 12;553(2):342-6
references.pmid: 1657284
references.citation: Behav Genet. 1989 May;19(3):387-407
references.pmid: 2757591