Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: Oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorderReportar como inadecuado

Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: Oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Biomedical Science

, 17:29

First Online: 21 April 2010Received: 01 February 2010Accepted: 21 April 2010DOI: 10.1186-1423-0127-17-29

Cite this article as: Kung, JC., Chen, TC., Shyu, BC. et al. J Biomed Sci 2010 17: 29. doi:10.1186-1423-0127-17-29


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.

AbbreviationsACnucleus accumbens

ANOVAanalysis of variance

BLAbasolateral nucleus of the amygdala

BNSTbed nucleus of the stria terminalis-supracapsular division

BSTLbed nucleus of the stria terminalis-lateral division

CA1CA1 field of the hippocampus

CA2CA2 field of the hippocampus

CeAcentral nucleus of amygdala

Cg-RScingulate-retrosplenial cortex

CSconditioned stimulus

DGdentate gyrus

Fos-LIFos-like immunoreactivity

ILinfralimbic cortex

LHlateral hypothalamus

M1primary motor cortex

MeAmedial nucleus of the amygdala

NGST3% normal goat serum containing 0.1% triton

PaLMparaventricular hypothalamic nucleus-lateral magnocellular part

PBSphosphate-buffered saline

PrLprelimbic cortex


PTSDposttraumatic stress disorder

PVTparaventricular thalamic nucleus

USunconditioned stimulus

VOnucleus of ventral orbital cortex


Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-17-29 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Jen-Chuang Kung - Tsung-Chieh Chen - Bai-Chuang Shyu - Sigmund Hsiao - Andrew Chih Wei Huang


Documentos relacionados