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.

Studies of the interaction between behavioral stereotypes and the effects of activation of presynaptic dopamine receptors during extinction and amnesia in mice.

The involvement of presynaptic dopamine receptors in the retention of a conditioned passive avoidance reflex through extinction and amnesia was studied in C57BL/6J mice selected in a 20-day aggressive conflict test for aggressive and submissive behavioral stereotypes. These experiments showed that in aggressive mice, activation of presynaptic receptors with the agonist (+)3-(3-hydroxyphenyl)-N-n-propylpiperidine [(+)3PPP] at a dose of 2 mg/kg degraded learning, significantly decreased the retention time of the acquired conditioned habit in extinction, and increased the effect of an amnesia-inducing treatment. Mice showing submissive behavior in daily confrontations with aggressors responded to administration of (+)3PPP with long-lasting reproduction of the conditioned passive avoidance reaction during extinction and showed no changes in the development of amnesia. These data on the relationship between the effects of activating presynaptic dopamine receptors in reproduction of the memory trace in conditions of trace disruption on the one hand and behavioral status on the other are assessed from the point of view of different basal levels of dopaminergic system operation in aggressive and submissive mice.