Regional Changes of Brain Serotonin and Its Metabolite 5-Hydroxyindolacetic Acid and Development of Immunosuppression in Submissive Mice

Abstract

The production of submissive behavior in C57BL/6J mice during 10 or 20 days of social confrontations resulted in increases in serotonin (5-HT) content in the amygdala, hippocampus, nucleus caudatus, Al1, A10, A9, and hypothalamus. The level of 5-hydroxyindolacetic acid (5-HIAA) was higher in most structures after 20 daily encounters compared to animals tested for 10 days. The ratio 5-HIAA/5-HT was increased in the nucleus raphe, accumbens, A9, and hypothalamus in mice displaying submission during 10 and 20 confrontations. The experience of defeats during 10 days accompanied with 5-HT system activation in a number of brain structures (nucleus raphe, accumbens, and A9) produced immunosuppression. With increasing number of confrontations the ratio 5-HIAA/5-HT was decreased in the same structures and a tendency to the immune response elevation appeared.

Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL/6 and CD-1 mice

“…For example, socially defeated mice had reduced mitogen-induced splenocyte proliferation, as compared with handled controls (Beitia et al, 2005). Similarly, splenocytes from socially defeated mice immunized with sheep red blood cells formed significantly fewer plaque-forming and rosetteforming cells than controls (Devoino et al, 2004). Defeat in the SDR model, however, causes an increase in the production of the proinflammatory cytokines IL-1α, IL-6, and TNF-α (Avitsur et al, 2002;Avitsur et al, 2003) and a marked insensitivity to the glucocorticoid hormone corticosterone ).…”

Dopamine D<sub>1</sub>- and D<sub>2</sub>-Receptors in Immunostimulation under Activation of Mu-Opioid Receptors in Mice with Different Psychoemotional States

“…Aggressive and depressive-like behaviors are known to be associated with changes in the level and distribution of serotonin (5-HT) and DA and their metabolites over brain structures [17,20,[30][31][32], which appeared to be involved in the mechanisms of immunomodulation [9,10,17]. There is also evidence for significant differences in immune reactivity of C57BL/6J mice engaged in aggression or depressive-like behavior [17,33].…”

“…There is also evidence for significant differences in immune reactivity of C57BL/6J mice engaged in aggression or depressive-like behavior [17,33]. Numerous data indicate that aggression is characterized by increasing activity of the DAergic system, known to stimulate immune functions, while depressive behavior is accompanied with changes in activity of the 5-HTergic system providing an inhibitory mechanism of immunomodulation [17,31,32].…”

Contribution of brain dopamine, serotonin and opioid receptors in the mechanisms of neuroimmunomodulation: Evidence from pharmacological analysis

“…At the same time, administration of both agonists did not change the number of AFC in submissive or depressive mice suggesting that 5-HT 1A -and 5-HT 2A -receptors are desensitized under formation of these types of behavior [78,82,83]. Furthermore, the development of submissive behavior and depressive-like states in mice of different strains has been shown to be accompanied by an increase in 5-HTergic activity over subcortical brain structures and considerable immunosuppression [19,57]. A selective activation of presynaptic 5-HT 1A -receptors with 8-OH-DPAT markedly increased the immune response level in the control mice and submissive CBA mice as well as in C57BL/6J mice with depressive-like state developed for 10 days of social stress [82,83].…”

“…At present changes in immunological variables have been also reported in animals displaying aggressive or submissive behaviors [19,[51][52][53][54][55], which are also known to be accompanied with changes in the level and distribution of neurotransmitters over brain structures [19,[56][57][58]. The majority of data indicate that aggression developed in different animal models is linked to an increase in activity of the DAergic system [6,19] and a higher immune responsiveness [19,[51][52][53]55], associated with growing numbers of CD4 + Th cells in the bone marrow [19].…”