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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,. | Kung et al. Journal of Biomedical Science 2010 17 29 http www.jbiomedsci.eom content 17 1 29 a NSC Tha cost of publication In Journal of Blomodlcal Science Is boms by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice Oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder Jen-Chuang Kung1 2 Tsung-Chieh Chen1 Bai-Chuang Shyu1 Sigmund Hsiao2 3 and Andrew Chih Wei Huang 4 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 .