Changes in serotonergic measures in whole blood and various brain regions of rats administered with the 5-HT1A agonist tandospirone and/or exposed to electric foot-shock.

We studied the effects of foot-shock on tryptophan, serotonin [5-hydroxytryptamine (5-HT)], and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in whole blood and various brain regions of rats pretreated with tandospirone, a novel 5-HT1A receptor agonist. The administration of tandospirone did not result in changes in serotonergic measures, but stress or stress plus the administration of tandospirone resulted in an increase in blood levels of tryptophan, 5-HT, and 5-HIAA. In animals given stress, tryptophan levels rose in every part of the brain, and in animals given stress and tandospirone, tryptophan levels increased in all the brain regions except the medulla. The administration of tandospirone alone did not give rise to changes in tryptophan levels in any part of the brain. The administration of tandospirone resulted in an increase in 5-HT levles in all brain regions except the cerebellum. In rats given stress and tandospirone, 5-HT levels increased in the hypothalamus, midbrain, and cortex relative to controls. In every part of the brain, the administration of tandospirone resulted in a decrease in the turnover rate of serotonin (5-HIAA/5-HT). In the presence of stress, the administration of tandospirone resulted in a decrease in the turnover rate of serotonin in hypothalamus, hippocampus, and midbrain compared with controls and stress alone. These results suggest that tandospirone may stimulate presynaptic receptors in the midbrain and inhibit the activity of monoamine oxidase, resulting in an increase in 5-HT levels in the serotonergic nerve terminals.