Social defeat stress exacerbates the blood abnormalities in Opisthorchis felineus-infected mice.

A model of chronic opisthorchiasis combined with social stress is examined; this situation is more likely for humans and animals than a separate impact of the infectious factor. For this purpose, we evaluated the effects of Opisthorchis felineus ("OP" group) and 30-day social stress (confrontations between males, "SS" group) alone and in combination ("OP + SS" group) in inbred C57BL/6 male mice and compared these effects according to the parameters listed below. The animals exposed to neither factor formed the control group ("CON"). All animals were assayed for blood biochemical parameters, changes in blood cell composition, and pattern of bone marrow hematopoiesis. By the end of the experiment, we have observed crucial effects of the two factors on the blood and liver of "OP" and "OP + SS". Eosinophil and basophil counts increased and relative segmented neutrophil and monocyte counts decreased in "OP + SS" mice on the background of activated myelopoiesis, mainly determined by social stress. Despite depressed erythropoiesis, "OP" mice displayed no changes in the relative peripheral erythrocyte counts. On the contrary, social stress, which stimulated erythropoiesis in "SS" and "OP + SS" mice, was accompanied by a decrease in the relative erythrocyte counts and hematocrit. Hepatosplenomegaly was observed on the background of these two impacts. Changes in transaminase (ALT and AST) and alkaline phosphatase activities as well as an increase in cholesterol and product of lipid peroxidation suggest a pronounced destruction of the liver. Altogether, social stress exacerbates many of the assayed blood parameters in the mice infected with the liver fluke.

Combined effects of social stress and liver fluke infection in a mouse model.

The effects of two influences, social stress and acute opisthorchiasis, were investigated in inbred C57BL/6J male mice. In the model of social stress, mice were repeatedly attacked and defeated by aggressive outbred ICR male mice and were in continuous sensory contact with an aggressive conspecific mouse in their home cage for 20 days. Acute opisthorchiasis was provoked by invasion of Opisthorchis felineus (50 larvae per animal) on the fourth day after the social stress was induced. Simultaneous action of both factors caused the hypertrophy of adrenal glands, as well as elevated the activity of cathepsins B and L in the spleen. This effect on the activity of the cysteine proteases in the hippocampus and hypothalamus following O. felineus invasion was the predominant result of simultaneous action with social stress. Acute opisthorchiasis, social stress, and their combination caused an increase in the level of blood IL-6 in approximately 30% of the animals. Social stress induced a more pronounced effect on mouse plus-maze behavior than O. felineus invasion. Our results suggest a more severe negative effect of the simultaneous influence of both factors on most of the parameters that were investigated.

Repeated positive fighting experience in male inbred mice.

Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions.

Effect of MAO A deficiency on different kinds of aggression and social investigation in mice.

Monoamine oxidase A (MAO A) degrades serotonin, dopamine and noradrenaline, factors critically involved in the regulation of aggression. Different kinds of aggression were investigated in Tg8, a transgenic mouse strain lacking a functional MAO A gene. MAO A-deficient mice differ from wild-type C3H/HeJ (C3H) in terms of showing higher territorial, predatory and isolation-induced aggression. Tg8 demonstrated shorter latencies to cricket killing and to the first attack after 6 weeks isolation than C3H mice. In the resident-intruder paradigm, MAO A-lacking mice were more aggressive than C3H when tested as intruders. In contrast to C3H, attack in Tg8 mice did not depend on different aggressiveness of intruders of BALB/c, A/Sn and C3H strains. Tg8 mice displayed no increase in aggression but demonstrated reduced social investigation towards anesthetized, as well as towards juvenile BALB/c males. Thus, MAO A deficiency in Tg8 mice is accompanied by increased expression of different kinds of aggression, as well as by disruption of normal pattern of social interaction.