title: Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder.
abstract: The present study used the preproenkephalin knockout (ppENK) mice to test whether the endogenous enkephalins deficit could facilitate the anxiety- and depressive-like symptoms of posttraumatic stress disorder (PTSD). On Day 1, sixteen wildtype (WT) and sixteen ppENK male mice were given a 3 mA or no footshock treatment for 10 seconds in the footshock apparatus, respectively. On Days 2, 7, and 13, all mice were given situational reminders for 1 min per trial, and the freezing response was assessed. On Day 14, all mice were tested in the open field test, elevated plus maze, light/dark avoidance test, and forced swim test. Two hours after the last test, brain tissues were stained to examine c-fos expression in specific brain areas. The present results showed that the conditioned freezing response was significant for different genotypes (ppENK vs WT). The conditioned freezing effect of the ppENK mice was stronger than those of the WT mice. On Day 14, the ppENK mice showed more anxiety- and depressive-like responses than WT mice. The magnitude of Fos immunolabeling was also significantly greater in the primary motor cortex, bed nucleus of the stria terminalis-lateral division, bed nucleus of the stria terminalis-supracapsular division, paraventricular hypothalamic nucleus-lateral magnocellular part, central nucleus of the amygdala, and basolateral nucleus of the amygdala in ppENK mice compared with WT mice. In summary, animals with an endogenous deficit in enkephalins might be more sensitive to PTSD-like aversive stimuli and elicit stronger anxiety and depressive PTSD symptoms, suggesting an oversensitivity hypothesis of enkephalin deficit-induced PTSD.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Jen-Chuang
authors.initials: JC
authors.lastname: Kung
authors.forename: Tsung-Chieh
authors.initials: TC
authors.lastname: Chen
authors.forename: Bai-Chuang
authors.initials: BC
authors.lastname: Shyu
authors.forename: Sigmund
authors.initials: S
authors.lastname: Hsiao
authors.forename: Andrew Chih Wei
authors.initials: AC
authors.lastname: Huang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D001362:Avoidance Learning; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D004195:Disease Models, Animal; D004597:Electroshock; D004745:Enkephalins / Q000172:deficiency* / Q000235:genetics; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D014018:Tissue Distribution
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; C033660:preproenkephalin
references.citation: Psychoneuroendocrinology. 2009 Jun;34(5):786-90
references.pmid: 19157714
references.citation: Arch Gen Psychiatry. 1993 Apr;50(4):295-305
references.pmid: 8466391
references.citation: Biol Psychiatry. 1998 Dec 15;44(12):1305-13
references.pmid: 9861473
references.citation: Pharmacol Biochem Behav. 2006 Oct;85(2):324-31
references.pmid: 17034840
references.citation: Trends Neurosci. 1995 Jan;18(1):22-9
references.pmid: 7535487
references.citation: Neurosci Biobehav Rev. 2004 Mar;28(1):65-94
references.pmid: 15036934
references.citation: Nature. 1996 Oct 10;383(6600):535-8
references.pmid: 8849726
references.citation: Brain Res. 1988 Apr 26;447(1):25-34
references.pmid: 2838129
references.citation: Biol Psychiatry. 2003 Feb 15;53(4):275-83
references.pmid: 12586446
references.citation: Compr Psychiatry. 2008 Sep-Oct;49(5):430-40
references.pmid: 18702929
references.citation: Eur J Pain. 2002;6(5):395-402
references.pmid: 12160514
references.citation: Psychoneuroendocrinology. 1997 Oct;22(7):517-29
references.pmid: 9373885
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2001 May;25(4):729-41
references.pmid: 11383975
references.citation: Prog Brain Res. 2008;167:151-69
references.pmid: 18037013
references.citation: Ann N Y Acad Sci. 1997 Jun 21;821:332-51
references.pmid: 9238215
references.citation: J Exp Psychol Anim Behav Process. 1992 Oct;18(4):400-13
references.pmid: 1402696
references.citation: Physiol Behav. 2007 Mar 16;90(4):687-95
references.pmid: 17254618
references.citation: Eur J Pharmacol. 1988 Apr 13;148(3):437-9
references.pmid: 2838307
references.citation: Neuroscience. 2008 Mar 27;152(3):703-12
references.pmid: 18308474
references.citation: Psychoneuroendocrinology. 2007 Jun;32(5):437-50
references.pmid: 17433558
references.citation: Psychoneuroendocrinology. 2008 Apr;33(3):282-91
references.pmid: 18164825
references.citation: Behav Brain Res. 2005 Feb 28;157(2):291-8
references.pmid: 15639180
references.citation: J Pharmacol Exp Ther. 1987 May;241(2):393-400
references.pmid: 3033214
references.citation: J Psychiatr Res. 2007 Nov;41(10):848-60
references.pmid: 17027033
references.citation: Pharmacol Biochem Behav. 1994 Mar;47(3):437-41
references.pmid: 7911573
references.citation: Biol Psychiatry. 1985 Mar;20(3):314-25
references.pmid: 2858226
references.citation: J Affect Disord. 2002 Jun;70(1):1-17
references.pmid: 12113915
references.citation: Psychopharmacol Bull. 1989;25(3):417-21
references.pmid: 2626517
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2004 Sep;28(6):923-35
references.pmid: 15380853
references.citation: Physiol Behav. 2008 Jun 9;94(3):341-8
references.pmid: 18339410
references.citation: Brain Res. 1991 Sep 13;559(1):109-17
references.pmid: 1664272
references.citation: Biol Psychiatry. 1996 Jan 15;39(2):129-34
references.pmid: 8717611
references.citation: Mol Psychiatry. 1996 Sep;1(4):278-97
references.pmid: 9118351
references.citation: Ann N Y Acad Sci. 1997 Jun 21;821:529-32
references.pmid: 9238245
references.citation: Biol Psychiatry. 2001 May 1;49(9):763-73
references.pmid: 11331084
references.citation: Biol Psychiatry. 2007 May 1;61(9):1030-8
references.pmid: 16945349
references.citation: Mol Pain. 2008 Sep 30;4:41
references.pmid: 18826595
references.citation: J Neurosci Res. 2005 Jul 1;81(1):140-52
references.pmid: 15931675
references.citation: Biol Psychiatry. 1993 Apr 1;33(7):479-86
references.pmid: 8513032
references.citation: N Engl J Med. 2002 Jan 10;346(2):108-14
references.pmid: 11784878
references.citation: Neuropsychopharmacology. 2000 Jan;22(1):77-88
references.pmid: 10633493
references.citation: Biol Psychiatry. 1999 Apr 1;45(7):806-16
references.pmid: 10202567
references.citation: Physiol Behav. 2006 May 30;87(5):881-90
references.pmid: 16546226