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Comparative Study
. 2014 Dec;17(6):471-83.
doi: 10.3109/10253890.2014.954104.

Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction

Caroline A Browne  1 , Joachim Hanke, Claudia Rose, Irene Walsh, Tara Foley, Gerard Clarke, Herbert Schwegler, John F Cryan, Deniz Yilmazer-Hanke
Affiliations
Comparative Study

Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction

Caroline A Browne et al. Stress. 2014 Dec.

Abstract

Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post-traumatic stress disorder.

Keywords: Acute swim stress; C3H/He; DBA/2; congenic-like recombinant inbred; dopamine; fear extinction; noradrenaline; serotonin.

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Figures

Figure 1
Figure 1
The D × H recombinant inbred mouse strains both have a DBA/2J background, but the high-fear sensitized startle (H-FSS) strain has an insertion of four chromosomal C3H/2JHd segments into the DBA/2JHd background compared to the low (L)-FSS strain. A: Increase in freezing duration following acclimation (0-2 min), and extinction learning during the first versus last 10 min of presentation of conditioned acoustic stimuli (CS). * p<0.05 for fear recall (acclimation vs. 3-12 min) and extinction learning (3-12 min vs. 13-22 min), ^ p<0.05 for strain differences, & p<0.05 strain × fear recall interaction. B: H-FSS mice also show a severe extinction deficit in their freezing response. # p<0.05 for strain differences. C: Brief freezing in individual L-FSS mice upon CS presentation that declines rapidly, whereas H-FSS mice show generalized fear responses during acclimation and a deficit in extinction learning.
Figure 2
Figure 2
Immobility in the acute-15 min variant of the forced swim test (FSTv) and endocrine changes 30 min after exposure to acute swim stress (15 min duration). A: The more fearful H-FSS mice spent a longer time immobile (i.e., floating) than the less fearful L-FSS mice in the acute FSTv. B: There were no significant differences between basal plasma corticosterone concentrations of H-FSS and L-FSS mice, but acute swim stress induced by exposure to the FSTv resulted in a significant increase in corticosterone levels in both strains. L-FSS mice showed a higher stress-induced increase in plasma corticosterone than H-FSS mice (% of control), but this difference was not significant at the time point investigated after exposure to acute swim stress. * p<0.05.
Figure 3
Figure 3
Basal noradrenaline levels and changes in noradrenaline 30 min after exposure to acute swim stress in the FSTv. The H-FSS mice display higher noradrenaline concentrations in the amygdala (A), medial prefrontal cortex (C), and hypothalamus (E), and lower NA concentrations in the striatum (D) than L-FSS mice, but the two mouse strains do not differ in hippocampal NA levels (B). A stress × strain interaction is seen in the hypothalamus (E), and a stress effect in the brainstem (F). ~ p<0.05 for stress effect, * p<0.05 for strain effect and ^ p<0.05 for stress × strain interaction in the two-way ANOVA.
Figure 4
Figure 4
Basal dopamine levels and changes in dopamine 30 min after exposure to acute swim stress in the FSTv. Dopamine levels are higher in the amygdala (A), hypothalamus (E), and brainstem (F) and lower in the striatum (D) of H-FSS than L-FSS mice. No differences are observed in the hippocampus (B). The stress-induced increase in dopamine levels is significant in the striatum (D) and brainstem (F), and an additional stress × strain interaction is seen in the medial prefrontal cortex (C) and striatum (D). ~ p<0.05 for stress effect, * p<0.05 for strain effect, and ^ p<0.05 for stress × strain interaction in the two-way ANOVA.
Figure 5
Figure 5
Basal serotonin levels and changes in serotonin 30 min after exposure to acute swim stress in the FSTv. Serotonin levels are higher in the amygdala (A) and hypothalamus (F) and lower in the striatum (D) of H-FSS than L-FSS mice. As with dopamine, no differences are observed in the hippocampus (B) and medial prefrontal cortex (C). The stress-induced increase in serotonin levels is significant in the amygdala (A) and brainstem (F), and a stress × strain interaction is seen in the hypothalamus (E). ~ p<0.05 for stress effect, * p<0.05 for strain effect, and ^ p<0.05 for stress × strain interaction in the two-way ANOVA.
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