Changes in brain serotonergic activity in anxious losers

Previous experiments showed that repeated experience of defeats in ten dail y agonistic confrontations produced pronounced anxiety in C57BL/6J male mic e (losers) as estimated by some plus-maze parameters and decreased communic ative behavior observed in the partition test (Avgustinovich et at, 1997). Tryptophan hydroxylase (TPH) activity and the levels of serotonin (5-HT) an d 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain, hypothalamus, amygda la, hippocampus and striatum have been measured and analysed in anxious los ers. The data showed that pronounced anxiety developing in losers was accom panied by changes of serotonin metabolism in the various brain areas differ ently. A lower 5-HIAA level and 5-HIAA/5-HT ratio in the hippocampus as wel l as lower 5-HIAA level and decreased TPH activity in the amygdala were fou nd in the anxious losers in comparison with the control (5 days of individu al housing). Elevated 5-HIAA level and 5-HIAA/5-HT ratio were shown in the midbrain of the losers. The increased TPH activity was found in the hypotha lamus of the losers. [H-3]8-OH-DPAT binding (B-max) was decreased in the lo sers' frontal cortex and amygdala but not changed in the midbrain. Flesinox an (0.5 mg/kg, i. p.), the 5-HT1A receptor agonist, was ineffective in chan ging the communicative behavior of the losers in the partition test. Reduce of brain 5-HT1A receptor sensitivity have been suggested in the anxious lo sers under influence of social defeats. It was suggested that the developme nt of pronounced anxiety in the losers due to the repeated social confronta tions is accompanied by hypoactivity of serotonergic system in the amygdala and hippocampus.