Journal List > Korean J Physiol Pharmacol > v.12(3) > 1025538

Park, Choi, Lee, Kang, Shin, Kim, Kim, Shin, Lee, and Shin: Effects of Repeated Citalopram Treatments on Chronic Mild Stress-Induced Growth Associated Protein-43 mRNA Expression in Rat Hippocampus

Abstract

Although growth associated protein-43 (GAP-43) is known to play a significant role in the regulation of axonal growth and the formation of new neuronal connections in the hippocampus, there is only a few studies on the effects of acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in GAP-43 mRNA expression in the hippocampus have not been explored before. To explore this question, male rats were exposed to acute immobilization stress or CMS. Also, citalopram was given prior to stress everyday during CMS procedures. Acute immobilization stress significantly increased GAP-43 mRNA expression in all subfields of the hippocampus, while CMS significantly decreased GAP-43 mRNA expression in the dentate granule cell layer (GCL). Repeated citalopram treatment decreased GAP-43 mRNA expression in the GCL compared with unstressed controls, but this decrease was not further potentiated by CMS exposure. Similar decreases in GAP-43 mRNA expression were observed in CA1, CA3 and CA4 areas of the hippocampus only after repeated citalopram treatment in CMS-exposed rats. This result indicates that GAP-43 mRNA expression in the hippocampus may differently respond to acute and chronic stress, and that repeated citalopram treatment does not change CMS-induced decreases in GAP-43 mRNA expression in the GCL.

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Fig. 1.
(A) The effects of acute stress on GAP-43 mRNA levels in CA1, CA3, CA4 and dentate granular cell layer (GCL) of the hippocampus (n=4 per group) (B) The effects of chronic mild stress (CMS) on GAP-43 mRNA levels in the CA1, CA3, CA4 and GCL of the hippocampus (n=7 per group). The results are expressed as percent of mean value from control group and are mean standard error of mean (S.E.M.). Data were compared by Student's t-test. ∗p<0.05, ∗∗p<0.01 and ∗∗∗p<0.001 vs. control group.
kjpp-12-117f1.tif
Fig. 2.
Representative autoradiographs of 35S-labeled GAP-43 mRNA expression in the hippocampus from each treatment group are shown. (A) control (B) acute immobilization stress.
kjpp-12-117f2.tif
Fig. 3.
The effects of repeated citalopram treatment and CMS on GAP-43 mRNA levels in the GCL. Repeated citalopram treatment and CMS significantly decreased GAP-43 mRNA levels in the GCL, but there was no significant interaction between repeated citalopram treatment and CMS. The results are expressed as percent of mean value from SAL+CON group and are mean±S.E.M (n=9 per group). Data were compared using a one-way ANOVA with Fisher's LSD post hoc test. ∗p<0.05 and ∗∗p<0.01 vs. saline-treated unstressed control (SAL+CON). Abbreviations used: citalopram treated unstressed group (CON+CIT), saline treated CMS-exposed group (CMS+SAL), citalopram treated CMS-exposed group (CMS+CIT).
kjpp-12-117f3.tif
Fig. 4.
Representative autoradiographs of 35S-labeled GAP-43 mRNA in the hippocampus from each treatment group are shown. (A) saline treated unstressed group (B) citalopram treated unstressed group (C) saline treated CMS-exposed group (D) citalopram treated CMS-exposed group.
kjpp-12-117f4.tif
Table 1.
Schedule of chronic mild stress
  Monday Tuesday Wednesday Thursday Friday
Morning Restraint 1 h Restraint 1 h Access to restricted food (3 g) for 2 h 1 h exposure to empty bottle, restraint 1 h Restraint 1 h
Afternoon Restraint 1 h, overnight illumination Restraint 1 h, overnight food and water deprivation Restraint 1 h, overnight water deprivation Restraint 1 h, group-housed in soiled cage overnight Reversed light-dark cycle throughout the weekend
Table 2.
Effect of chronic mild stress and repeated citalopram treatment on the GAP-43 mRNAs levels in rat hippocampus
  CON+SAL CON+CIT CMS+SAL CMS+CIT
CA 1 100.0±7.6 96.5±3.0 107.4±3.0 88.1±7.3
CA 3 100.0±4.3 97.4±1.1 106.1±2.6 86.3±4.8
CA 4 100.0±3.4 99.8±1.6 105.7±2.4 86.1±4.8∗

The results are expressed as percent of mean value from SAL+CON group and are mean±S.E.M (n=9 per group). Data were compared using a one-way ANOVA with Fisher's LSD post hoc test. ∗p<0.05 and ∗∗p<0.01 vs. saline-treated unstressed control (SAL+CON). Abbreviations used are the same as those in Fig. 3.

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