Cole J C, Burroughs G J, Laverty C R, Sheriff N C, Sparham E A, Rodgers R J
Department of Psychology, University of Leeds, UK.
Psychopharmacology (Berl). 1995 Apr;118(4):425-36. doi: 10.1007/BF02245943.
The influence of alpha 2-adrenoceptor antagonists in animal models of anxiety is quite inconsistent, with results spanning the full range of effect from anxiogenesis to anxiolysis. In the present study, an ethological technique was used to examine the effects of yohimbine (0.5-4.0 mg/kg) on plus-maze behaviour in DBA/2 mice. Results indicated significant anxiolytic-like effects on standard spatiotemporal measures at 2.0-4.0 mg/kg, and on risk assessment measures across the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains confirmed that this action of yohimbine in the murine plus-maze is not peculiar to DBA/2 mice. The more selective alpha 2-adrenoceptor antagonist, idazoxan (0.63-5.0 mg/kg), exerted much weaker behavioural effects in the maze while the alpha 2-adrenoceptor agonist, clonidine (0.01-0.1 mg/kg), produced a profile consistent with non-specific behavioural disruption. Data are discussed in relation to the possible involvement of 5-HT1A receptor mechanisms in the observed anxiolytic-like effects of yohimbine in the murine plus-maze.
α2-肾上腺素能受体拮抗剂在焦虑动物模型中的影响相当不一致,结果涵盖了从促焦虑到抗焦虑的全部效应范围。在本研究中,采用行为学技术检测育亨宾(0.5 - 4.0毫克/千克)对DBA/2小鼠在高架十字迷宫行为的影响。结果表明,在2.0 - 4.0毫克/千克剂量下,育亨宾对标准时空指标具有显著的抗焦虑样效应,并且在整个剂量范围内对风险评估指标也有影响。对T1和BALB/c品系进行的全面后续研究证实,育亨宾在小鼠高架十字迷宫中的这种作用并非DBA/2小鼠所特有。选择性更强的α2-肾上腺素能受体拮抗剂咪唑克生(0.63 - 5.0毫克/千克)在迷宫中产生的行为效应要弱得多,而α2-肾上腺素能受体激动剂可乐定(0.01 - 0.1毫克/千克)产生的行为表现与非特异性行为干扰一致。结合5-HT1A受体机制可能参与育亨宾在小鼠高架十字迷宫中所观察到的抗焦虑样效应这一情况,对数据进行了讨论。