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<= NON-STRESSED CONTROLS

STRESSED CONTROLS = FLUOXETINE (10 mg/kg ip) =■ SSR149415 (30 mg/kg ip)

Fig. 3. Effects of repeated administration of the Vlb receptor antagonist, SSR149415, and the 5-HT reuptake inhibitor, fluoxetine, on chronic mild stress-induced (A) degradation of the physical state of the coat of animals, (B) anxiogenic-like behavior in the light/dark tests, and (C-F) increased defensiveness as measured in the defense test battery when mice are confronted with a rat. Flight responses were measured when the rat first approached the mouse; risk assessment was observed when mice were chased by the rat; defensive aggression occurred upon forced contact with the rat; and mice displayed anticipatory anxiety after the removal of the rat from the test arena. The chronic mild stress protocol consists of the sequential application of a variety of mild stressors, including restraint, forced swimming, water deprivation, pairing with another stressed animal, in a schedule that lasts for three weeks, and is repeated thereafter. The drugs were administered intraperitoneally once a day for four weeks. Data represent mean±S.E.M. *P<0.05 (vs stressed mice); § P<0.05 (vs nonstressed mice).

period, animals treated with SSR149415 displayed a comparable physical state as nonstressed controls. In addition, the drug was able to prevent the stress-induced increase in anxiety levels in the light/dark test (Fig. 3B), and reduced defensive reactions in the MDTB, as did the prototypical antidepressant, fluoxetine (Fig. 3C-F).

To investigate further the antidepressant potential of Vlb receptor blockade, SSR149415 was tested in the chronic subordination stress model in rats (Blanchard et al, 2002). Effects were compared to those obtained with fluoxetine in this test. In mixed-sex rat groups, consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males can be differentiated from

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