Chronic mild stress alters the somatostatin receptors in the rat brain

Abstract

Rationale: The involvement of somatostatin (SST) and its receptors in the pathophysiology of depression and stress has been evidenced by numerous studies.

Objectives: The purpose of the present study was to find whether chronic mild stress (CMS), an animal model of depression, affects the SST receptors in the rat brain and pituitary, as well as the level of SST in plasma.

Methods: In CMS model, rats were subjected to 2 weeks of stress and behaviorally characterized using the sucrose consumption test into differently reacting groups based on their response to stress, i.e., stress-reactive (anhedonic), stress-non-reactive (resilient), and invert-reactive rats (characterized by excessive sucrose intake). We measured specific binding of [125I]Tyr3-Octreotide, expression of mRNA encoding sst2R receptors in the rat brains, expression of SST and its receptors in rat pituitary, and the level of SST in the plasma.

Results: The obtained results show decreases in binding of [125I]Tyr3-Octreotide in most of rat brain regions upon CMS and no significant differences between three stressed groups of animals, except for significant up-regulation of sst2 receptor in medial habenula (MHb) in the stress-reactive group. In the same group of animals, significant increase in plasma SST level was observed.

Conclusions: There are two particularly sensitive sites distinguishing the response to stress in CMS model. In the brain, it is MHb, while on the periphery this predictor is SST level in plasma. These changes may broaden an understanding of the mechanisms involved in the stress response and point to the intriguing role of MHb.

Fig. 1

The scheme of 2 weeks of CMS procedure. In the final baseline test after 2 weeks of stress, sucrose intakes were significantly different between the controls and the stressed animals (F(1,40) = 21.11, p < 0.0001). The graph shows the differences in sucrose intake after 2 weeks of stress. The data represents mean ± S.E.M., n = 10 animals per group. For statistical analysis, a one-way ANOVA test was used with a Bonferroni post hoc test

Fig. 2

Representative autoradiograms of binding [¹²⁵I]SST-28 in rat brains after 2 weeks of CMS procedure. C—control group, SR—stress-reactive group, SNR—stress non-reactive group, SIR—stress invert-reactive group, NS—non specific binding obtained using 1 μM SST14 non labeled rat somatostatin-14. Brain structures were selected using the Rat Brain Atlas Paxinos and Watson

Fig. 3

The percentage of specific binding of [¹²⁵I]Tyr³-Octreotide in selected rat brain structures after 2 weeks of CMS procedure. The data represent mean ± S.E.M., n = 10 animals per group. For statistical analysis, a one-way ANOVA test was used with a Bonferroni post hoc test. Asterisks indicate statistical significance vs. control group; *p < 0.05, **p < 0.01, ***p < 0.001; #p < 0.01 statistical significance vs. stress reactive group (stress R)

Fig. 4

The level of mRNA encoding sst2R in rat brains after 2 weeks of CMS. a Representative autoradiogram of in situ hybridization of sst2R mRNA. b The level of sst2R mRNA in the rat brains. Data are expressed as a mean of optical density (O.D.; means ± S.E.M.; n = 10 animals per group). For statistical analysis, a one-way ANOVA test was used with a Bonferroni post hoc test. *p < 0.05, **p < 0.01 vs. control group, ^$ p < 0.01 vs. stress R, ^# p < 0.01 vs. stress non-reactive (stress NR) group

Fig. 5

The plasma levels of SST in rats after 2 weeks of CMS procedure. Data represents means ± S.E.M.; n = 10 animals per group. For statistical analysis, a one-way ANOVA test was used with a Bonferroni post hoc test. Asterisks **p < 0.01 indicate statistical significance vs. control group; #p < 0.05 statistical significance vs. stress reactive group (stress R)