Abstract
A growing body of evidence showed that environmental enrichment (EE) ameliorated footshock-induced fear behavior of posttraumatic stress disorder (PTSD). However, no research comprehensively tested the effect of EE, cue, and the combination of EE and cue in footshock-induced fear behavior of PTSD symptoms. The present study addressed this issue and examined whether the medial prefrontal cortex (mPFC, including the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL)), the nucleus accumbens (NAc), the basolateral amygdala (BLA), and the hippocampus (e.g., CA1, CA3, and dentate gyrus (DG)) regulated the amelioration of the EE, cue, or the combination of EE and cue. The results showed that EE or cue could reduce fear behavior. The combination of EE and cue revealed a stronger decrease in fear behavior. The cue stimulus may play an occasion setting or a conditioned stimulus to modulate the reduction in fear behavior induced by footshock. Regarding the reduction of the EE in fear behavior, the Cg1 and IL of the mPFC and the NAc upregulated the c-Fos expression; however, the BLA downregulated the c-Fos expression. The mPFC (i.e., the Cg1, PrL, and IL) and the hippocampus (i.e., the CA1, CA3, and DG) downregulated the c-Fos expression in the suppression of the cue in fear behavior. The interaction of EE and cue in reduction of fear behavior occurred in the Cg1 and NAc for the c-Fos expression. The data of c-Fos mRNA were similar to the findings of the c-Fos protein expression. These findings related to the EE and cue modulations in fear behavior may develop a novel nonpharmacological treatment in PTSD.
Highlights
Posttraumatic stress disorder (PTSD) is a complicated mental illness [1]
To examine the effect of environmental enrichment and cue in freezing behavior of the PTSD animal model, a 2 × 2 × 3 three-way mixed analysis of variance (ANOVA) analysis indicated that significant differences occurred in the factor of EE (F ð1, 20Þ = 70:73, p < 0:05), cue (F ð1, 20Þ = 14:14, p < 0:05), and session (F ð2, 40Þ = 27:95, p < 0:05)
In post hoc Tukey’s Honest Significant Difference (HSD) tests, the results showed that the no environmental enrichment (no EE)/cue group was significantly decreased in the c-Fos expression than the no EE/no cue group (p < 0:05); the EE/no cue was significantly increased in the c-Fos expression compared to the no EE/cue group (p < 0:05; Figure 11(b))
Summary
Posttraumatic stress disorder (PTSD) is a complicated mental illness [1]. PTSD individuals often encounter a variety of psychiatric symptoms that include feeling fear, helplessness, horror, increased arousal, autonomic hyperarousal activities, fear sensitization, serious startle responses, hypervigilance, insomnia, irritability, and impaired concentration [2,3,4]. Concerning the numerous symptoms of PTSD, the fear symptom through classical conditioning to form fear memory in the animal model of PTSD effectively simulated the PTSD’s human symptoms [5]. In light of the previous studies, environmental enrichment (EE) exposures can effectively reduce the PTSD symptoms in the animal model [6,7,8,9,10,11]. EE reduced anxiety due to differentially activating the serotonin system and neuropeptide system in the PTSD animal model [11]. Chronic EE exposures reduced neonatal isolation-induced contextual freezing; chronic EE exposures did not affect single prolonged stress-related to anxiety behaviors or analgesia
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