CHARACTERISTICS OF ACTIVITY OF SEROTONERG IC BRAIN SYSTEM IN NATURAL AND PATHOLOGICAL ANXIETY IN MICE - STRAIN DIFFERENCES

Anxiety was estimated in intact male mice of C57BL/6J (C57) and (CBA) and CBA/Lac (CBA) strains and in males of both strains after the repea ted experience of social defeats (losers) in 10 daily aggressive confr ontations. A plus-maze test for behavior in a novel situation and a pa rtition test for communicative activity were applied. Tryptophan hydro xylase (TPH) activity, 5-hydroxytryptamine (5-HT) and 5-hydroxyindolea cetic acid (5-HIAA) levels were measured in the midbrain, hypothalamus , amygdala, hippocampus, and striatum in losers and controls (5 days o f individual housing of intact animals). Intact C57 mice which demonst rated active avoidance in the maze had reduced TPH activity in the all studied brain regions compared to the intact CBA mice with passive be havior. The 5-HT catabolism in intact C57 was lower in the midbrain an d hypothalamus and higher in amigdala, hippocampus, and striatum than in CBA mice. Chronic social stress led to expressed anxiety revealed b y both tests in C57 losers in contrast to CBA ones. This anxiety was a ccompanied by an increase in 5-HIAA level and 5-HIAA/5-HT ratio in the midbrain as well as by an increase in 5-HT level and decrease in 5-HI AA level and 5-HIAA/5-HT ratio in the hippocampus of C57 losers in com parison with the controls. Flesinoxan (0.5 mg/kg, i.p.), 5-HT1A recept or agonist,, changed the communicative behavior of controls but was in effective in losers. Thus, a decrease in sensitivity of 5-HT1A recepto rs was suggested in stress-induced anxiety of C57 losers. The less exp ressed anxiety in CBA losers was associated with less expressed change s in serotonergic metabolism. It is concluded that serotonergic mechan isms of pathological anxiety induced by the long-term social stress an d those of natural anxiety in intact mice are different.