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Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is the primary endocrine system to respond to stress. The HPA axis may be affected by increased level of corticotrophin-releasing factors under chronic stress and by chronic administration of monosodium glutamate (MSG). The purpose of this study was to investigate whether chronic MSG administration aggravates chronic variable stress (CVS)-induced behavioral and hormonal changes. Twenty-four adult male Sprague-Dawley rats, weighing 200∼220 g, were divided into 4 groups as follows: water administration (CON), MSG (3 g/kg) administration (MSG), CVS, and CVS with MSG (3 g/kg) administration (CVS+MSG). In addition, for the purpose of comparing the effect on plasma corticosterone levels between chronic stress and daily care or acute stress, 2 groups were added at the end of the experiment; the 2 new groups were as follows: naïve mice (n=7) and mice exposed to restraint stress for 2 h just before decapitation (A-Str, n=7). In an open field test performed after the experiment, the CVS+MSG group significant decrease in activity. The increase in relative adrenal weights in the CVS and CVS+MSG group was significantly greater than those in the CON and/or MSG groups. In spite of the increase in the relative adrenal weight, there was a significant decrease in the plasma corticosterone levels in the CVS+MSG group as compared to all other groups, except the naïve group. These results suggest that impaired HPA axis function as well as the decrease in the behavioral activity in adult rats can be induced by chronic MSG administration under CVS rather than CVS alone.
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Fig. 1.
Time-dependent changes of body weight in each group for 7 weeks. ∗Denotes significant differences among groups based on the one-way ANOVA and Bonferroni test (∗p<0.05). There are significant differences in the body weight between CON and other groups; an especially remarkable decrease could be seen in the CVS +MSG group. CON, control; MSG, monosodium glutamate; CVS, chronic variable stress.
Fig. 2.
Time-dependent changes of food consumption in each group for 7 weeks. ∗Denotes significant differences among groups based on the one-way ANOVA and Bonferroni test (∗p<0.05). There are significant differences in the daily food intake between the control (CON) and other groups. The difference in food intake between the groups gradually decreased during the course of the experiment, except in the CON group. CON, control; MSG, monosodium glutamate; CVS, chronic variable stress.
Fig. 3.
Behavioral response before the stress experiment in the open field test. The stereotypic and exploring activity gradually decreased as time passed in all groups. There is no significant difference in all parameters between the groups. CON, control; MSG, monosodium glutamate; CVS, chronic variable stress.
Fig. 4.
Behavioral response after the stress experiment in the open field test. There are significant differences in all parameters between the groups, especially the rats in the CVS+MSG group showed a remarkable decrease in their activity in the stereotypic count measurement. ∗Denotes significant differences among the groups based on the one-way ANOVA and Bonferroni test (∗p <0.05). CON, control; MSG, monosodium glutamate; CVS, chronic variable stress.
Fig. 5.
Relative adrenal weight following administration of MSG for 7 weeks. Statistical analysis was performed by the one-way ANOVA and Bonferroni test. The relative adrenal weight to body weight ratio was significantly higher in the CVS and CVS + MSG group than in the CON group. In addition, although there was no significant difference in the relative adrenal weight between the MSG and CVS group, the relative adrenal weight in the CVS + MSG group (0.75±0.09) was significantly higher than in the MSG group. ∗Denotes significant differences between CON and other groups (∗p <0.05). †Denotes significant difference between the stress and CVS + MSG group (†p<0.05). #Denotes significant difference between the MSG and CVS + MSG group (#p<0.05). CON, control; MSG, monosodium glutamate; CVS, chronic variable stress; A-Str, restraint stress for 2 hours just before decapitation; Wt, weight.
Fig. 6.
Plasma corticosterone levels in each group following 7 weeks experiment. Statistical analysis was performed by the one-way ANOVA and Bonferroni test. There was a significant difference in the plasma corticosterone levels between the naïve group and all other groups, including the CON group. $Denotes significant differences between the naïve and other groups ($p<0.05). ∗Denotes significant difference between CON and other groups (∗p <0.05). †Denotes significant difference between CVS + MSG and A-Str group (†p<0.05). CON, control; MSG, monosodium glutamate; CVS, chronic variable stress; A-Str, restraint stress for 2 hours just before decapitation.
Table 1.
Chronic variable stress protocol
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