Nature of the distribution of serotonin and a serotonin metabolite in brain structures and the development of immunosuppression in submissive mice.

Studies of C57BL/6J mice with acquired submissive behavior in a sensory contact model demonstrated increases in serotonin (5-HT) levels in the amygdaloid complex, hippocampus, the dopaminergic nuclei A11, A10, and A9, and in the caudate nucleus and hypothalamus, compared with controls, after 10 and 20 days of confrontations. Levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) in most structures were significantly higher after 20 days of confrontations than after 10 days. Increases in the 5-HIAA/5-HT ratio in the cervical nuclei of the midbrain, nucleus accumbens, A9, and hypothalamus as compared with controls were seen in mice with 10 and 20 days of confrontations. Immunization of mice on days 10 and 20 of confrontations showed suppression of immune responses as compared with controls, while immune measures reached control values by 40 days of experience of defeat. Thus, experience of 10 days of defeat led to immunosuppression on a background of activation of the 5-HT system in a series of brain structures: the cervical nuclei of the midbrain, the nucleus accumbens, and A9. As confrontations continued, there were decreases in the 5-HIAA/5-HT ratio on these structures, along with a tendency for immune responses to increase.

Brain content of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid and immune response in aggressive C57bl/6J mice.

Catabolism of 5-hydroxytryptamine in the midbrain raphe nuclei of aggressive C57Bl/6J mice increased after 10 and 20 days of confrontations. Both catabolism and concentration of 5-hydroxytryptamine increased in the dopaminergic nuclei A11, A10, A9, and in the amygdala. The level of 5-hydroxyindoleacetic acid in the A9 and raphe nuclei decreased after 20 days of confrontations, which coincided with manifestation of the immune response.

Molecular basis of the activity of the dopamine synapse in the mechanisms of learning and amnesia.

The neurochemical correlates of dopamine synapse activity were studied during the retrieval of memory traces and in the absence of retrieval ("psychogenic" amnesia). The physiochemical parameters of D2 receptor function, the synaptic membrane, and the catechol content were assessed in various regions of the brain (striatum, neostriatum, hypothalamus, amygdala, frontal cortex, hippocampus, nucleus accumbens, and nuclei A9 and A10) in intact, trained, and amnesiac rats. It was demonstrated that disturbances in memory trace retrieval were associated with decreased activation of synaptic dopamine receptors and alterations in the dopamine transformation pathway in the rat brain.

Regional brain patterns of dopamine, metabolites and D2 receptors in memory.

Patterns of dopamine (DA), 3,4-dihydroxyphenyl acetic (DOPAC), and homovanillic (HVA) acids, para-tyramine (p-TA), and D2 receptors for eleven structures of forebrain and midbrain were examined at 1 and 6 days after one trial passive avoidance training of rats, at 1 day after "psychogenic" amnesia production, immediately following training, and at the last day after foot shock of rats with previous "psychogenic" amnesia administration. Essential dopaminergic differences have been found between the groups studied. More significant neurochemical changes were observed in rats from trained and retrieval training groups. Regional DA changes were accompanied by a diminution of DA metabolism, an increase of D2 receptor density and p-TA. These neurochemical alterations differentially characterized the regional neurochemical patterns found in rat's exhibition nonretention (trained), forgetting, and amnesia. It is suggested that the present data reflect the existence of quantitative relationships between D2 receptors, DA, and p-TA, which are probably important in modulation of memory.