title: Hippocampal adult neurogenesis is enhanced by chronic eszopiclone treatment in rats.
abstract: The adult hippocampal dentate gyrus (DG) exhibits cell proliferation and neurogenesis throughout life. We examined the effects of daily administration of eszopiclone (Esz), a commonly used hypnotic drug and gamma-aminobutyric acid (GABA) agonist, compared with vehicle, on DG cell proliferation and neurogenesis, and on sleep-wake patterns. Esz was administered during the usual sleep period of rats, to mimic typical use in humans. Esz treatment for 7 days did not affect the rate of cell proliferation, as measured by 5-bromo-2'-deoxyuridine (BrdU) immunostaining. However, twice-daily Esz administration for 2 weeks increased survival of newborn cells by 46%. Most surviving cells exhibited a neuronal phenotype, identified as BrdU-neuronal nuclei (NeuN) double-labeling. NeuN is a marker of neurons. Non-rapid eye movement sleep was increased on day 1, but not on days 7 or 14 of Esz administration. Delta electroencephalogram activity was increased on days 1 and 7 of treatment, but not on day 14. There is evidence that enhancement of DG neurogenesis is a critical component of the effects of antidepressant treatments of major depressive disorder (MDD). Adult-born DG cells are responsive to GABAergic stimulation, which promotes cell maturation. The present study suggests that Esz, presumably acting as a GABA agonist, has pro-neurogenic effects in the adult DG. This result is consistent with evidence that Esz enhances the antidepressant treatment response of patients with MDD with insomnia.
authors.affiliation: Department of Psychology, UCLA, Los Angeles, CA, USA.
authors.forename: Melvi
authors.initials: M
authors.lastname: Methippara
authors.forename: Tariq
authors.initials: T
authors.lastname: Bashir
authors.forename: Natalia
authors.initials: N
authors.lastname: Suntsova
authors.forename: Ron
authors.initials: R
authors.lastname: Szymusiak
authors.forename: Dennis
authors.initials: D
authors.lastname: McGinty
mesh_terms: D000818:Animals; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D000069582:Eszopiclone; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D000069582:Eszopiclone
references.citation: Biol Psychiatry. 2006 Jun 15;59(12):1136-43
references.pmid: 16797263
references.citation: Sleep. 2008 Jul;31(7):1043-51
references.pmid: 18652100
references.citation: BMC Psychiatry. 2007 Aug 21;7:42
references.pmid: 17711589
references.citation: J Neurophysiol. 2005 Dec;94(6):4224-33
references.pmid: 16014798
references.citation: Psychopharmacology (Berl). 1997 Mar;130(2):139-43
references.pmid: 9106911
references.citation: Biol Psychiatry. 2006 Jun 1;59(11):1052-60
references.pmid: 16581036
references.citation: Nature. 2006 Feb 2;439(7076):589-93
references.pmid: 16341203
references.citation: Anesth Analg. 2008 Jun;106(6):1772-7
references.pmid: 18499608
references.citation: Eur J Neurosci. 2005 Oct;22(8):2111-6
references.pmid: 16262649
references.citation: Science. 2003 Aug 8;301(5634):805-9
references.pmid: 12907793
references.citation: Int J Neuropsychopharmacol. 2010 Jul;13(6):759-74
references.pmid: 19775499
references.citation: Sleep. 2007 Aug;30(8):959-68
references.pmid: 17702264
references.citation: Mol Cell Neurosci. 2005 Jun;29(2):181-9
references.pmid: 15911343
references.citation: J Neurosci. 2000 Dec 15;20(24):9104-10
references.pmid: 11124987
references.citation: Anat Rec. 1991 Dec;231(4):482-97
references.pmid: 1793176
references.citation: Neuron. 2005 Sep 15;47(6):803-15
references.pmid: 16157276
references.citation: J Neurosci. 1992 Sep;12(9):3642-50
references.pmid: 1527603
references.citation: Nat Rev Neurosci. 2006 Mar;7(3):179-93
references.pmid: 16495940
references.citation: Brain Res. 2005 Dec 14;1065(1-2):53-9
references.pmid: 16309630
references.citation: Neuroscience. 2007 Oct 26;149(2):273-85
references.pmid: 17900815
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 May;294(5):R1693-703
references.pmid: 18287218
references.citation: Sleep. 2003 Nov 1;26(7):793-9
references.pmid: 14655910
references.citation: Ann N Y Acad Sci. 2007 Jan;1096:157-69
references.pmid: 17405927
references.citation: J Neurophysiol. 2005 Dec;94(6):4528-32
references.pmid: 16033936
references.citation: Brain Res. 2008 Sep 4;1228:14-9
references.pmid: 18616933
references.citation: Biol Psychiatry. 2007 Mar 15;61(6):806-12
references.pmid: 17210135
references.citation: Am J Psychiatry. 2003 Mar;160(3):577-9
references.pmid: 12611844
references.citation: J Med Chem. 2008 Nov 27;51(22):7243-52
references.pmid: 18973287
references.citation: J Clin Sleep Med. 2007 Feb 15;3(1):48-55
references.pmid: 17557453
references.citation: Nat Rev Neurosci. 2002 Sep;3(9):728-39
references.pmid: 12209121
references.citation: Arch Gen Psychiatry. 2007 Feb;64(2):193-200
references.pmid: 17283286
references.citation: J Neurosci. 2007 Mar 21;27(12):3252-9
references.pmid: 17376985
references.citation: Brain Res. 2009 Mar 9;1259:26-31
references.pmid: 19138676
references.citation: Am J Psychiatry. 2002 Apr;159(4):663-5
references.pmid: 11925309
references.citation: Nat Neurosci. 2007 Sep;10(9):1110-5
references.pmid: 17726477
references.citation: Neuroscience. 1994 Jul;61(2):203-9
references.pmid: 7969902
references.citation: JAMA. 1989 Sep 15;262(11):1479-84
references.pmid: 2769898
references.citation: Arch Gen Psychiatry. 2004 Jul;61(7):705-13
references.pmid: 15237082
references.citation: Neuroscience. 2005;134(3):721-3
references.pmid: 16054767
references.citation: Annu Rev Neurosci. 2005;28:223-50
references.pmid: 16022595
references.citation: Neuropharmacology. 2009 May-Jun;56(6-7):994-1000
references.pmid: 19217915
references.citation: J Neuroendocrinol. 2002 May;14(5):397-402
references.pmid: 12000545
references.citation: Trends Neurosci. 2004 Aug;27(8):447-52
references.pmid: 15271491
references.citation: Int J Neuropsychopharmacol. 2009 Nov;12(10):1421-8
references.pmid: 19775501
references.citation: Sleep. 2008 Feb;31(2):259-70
references.pmid: 18274274
references.citation: Curr Opin Neurobiol. 2004 Apr;14(2):186-91
references.pmid: 15082323
references.citation: Neuroscience. 2007 Aug 10;148(1):325-33
references.pmid: 17630219
references.citation: Mol Psychiatry. 2000 May;5(3):262-9
references.pmid: 10889528
references.citation: Arch Gen Psychiatry. 2002 Jun;59(6):521-9
references.pmid: 12044194
references.citation: Nat Med. 1998 Nov;4(11):1313-7
references.pmid: 9809557
references.citation: J Pharmacol Sci. 2004 Mar;94(3):246-51
references.pmid: 15037809
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17501-6
references.pmid: 17088541
references.citation: J Comp Neurol. 2001 Jul 9;435(4):406-17
references.pmid: 11406822
references.citation: Arch Gen Psychiatry. 1999 Nov;56(11):1043-7
references.pmid: 10565505
references.citation: Am J Psychiatry. 2004 Feb;161(2):368-70
references.pmid: 14754790
references.citation: Hippocampus. 2006;16(3):296-304
references.pmid: 16411241
references.citation: Neurobiol Aging. 2005 Jan;26(1):103-14
references.pmid: 15585350
references.citation: Int J Neuropsychopharmacol. 2008 Mar;11(2):255-60
references.pmid: 17625025
references.citation: Eur J Neurosci. 2009 Jan;29(2):244-52
references.pmid: 19200231