α-Adrenoceptor Involvement in Swim Stress-induced Antinociception in the Mouse

Abstract

Abstract Three different intensities of swim stress produced stress-induced antinociception (SIA) in mice which was assessed either by the reduction in the number of abdominal constrictions produced by acetic acid or by an increase in reaction time on a hot-plate. The involvement of α-adrenoceptors in the three models of SIA was investigated using selective antagonists. SIA produced by the mild stress of a 30 s warm water swim was attenuated by idazoxan (0.5-1 mg kg−1), and by yohimbine at a dose (1 mg kg−1) which reduced antinociception produced by clonidine (12.5–50 μg kg−1). Indoramin (1–2 mg kg−1) did not affect this model of SIA, but reversed phenylephrine induced inhibition of the constrictions. A 3 min room temperature swim increased reaction times on the hot-plate and this naloxone-sensitive SIA was reduced significantly by prazosin (1–2 mg kg−1), idazoxan (0.5-1 mg kg−1) and yohimbine (0.5-1 mg kg−1) but enhanced by clonidine (0.5 mg kg−1) and noradrenaline (NA) (10 μg i.c.v.). Mice treated with 6-hydroxydopamine (60 + 60 μg i.c.v.) were hypersensitive to the hot-plate and did not develop SIA. Levels of noradrenaline in the brain (minus the cerebellum) were decreased after the room temperature swim SIA. The most severe stress of a cold water swim produced SIA on the hot-plate which was initially naloxone-insensitive. Both components of the cold water swim SIA were enhanced by NA (10 μg i.c.v.) and reduced by yohimbine (5 μg i.c.v.) whilst prazosin (5 μg i.c.v.) inhibited only the later naloxone-sensitive component; and these adrenoceptor agents potentiated cold water swim hypothermia induced by the cold water swim. These results show the differential involvement of α1-and α2-adrenoceptors in SIA in the mouse.