Influence of forced swimming stress on 5-HT_1A receptors and serotonin levels in mouse brain

Several stressful factors are able to modify 5-HT_1A receptors; for example, different schemes of forced swimming-induced stress (FS) produce a variety of changes in synthesis as well as in 5-HT_1A binding in the brain. In addition, it is known that the concentration of 5-HT in the brain is modified as a consequence of acute stressing. The main purpose of this study was to characterize the influence of 15 min of FS on 5-HT levels and on 5-HT _1A receptor density in specific brain areas. Mice stressed 24 h before were sacrificed and their brains processed by means of a quantitative autoradiography technique. The following areas were studied: dorsal raphe nucleus (DRN); median raphe nucleus (MRN); thalamus; hypothalamus; amygdala, and hippocampus. 5-HT and 5-hydroxyindolacetic acid (5-HIAA) concentrations in the brainstem, thalamus-hypothalamus, and hippocampus of stressed (ST) mice were analyzed 24 h after stressing by high performance liquid chromatography (HPLC) with fluorometric detection. All data were compared with corresponding unstressed (UST) controls. A significant decrease in 5-HT_1A receptor density in DRN, MRN, and hippocampus, accompanied by an increase in labeling of 5-HT_1A receptor in thalamus, hypothalamus, and amygdala was observed in ST animals. FS induced a decrease in the 5-HT concentration in the thalamus-hypothalamus, accompanied by an increase in hippocampus areas without affecting 5-HT concentration in the brainstem. Additionally, 5-HIAA/5-HT ratio in the thalamus-hypothalamus area was increased. This study showed that stress alters both 5-HT concentration and 5-HT_1A receptors in a region-specific manner.