Macy J D, Beattie T A, Morgenstern S E, Arnsten A F
Sections of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520-8016, USA.
Comp Med. 2000 Aug;50(4):419-25.
Self-injurious behavior (SIB) affects 0.8 to 10% of individually housed non-human primates, and is a substantial threat to their health and well being. The potential for SIB to involve multiple neurotransmitters and the complex variations in response to external stressors complicate case management. Modulation of the adrenergic system by use of guanfacine, an alpha2A-adrenergic receptor agonist, was assessed as a novel therapeutic strategy for SIB.
The efficacy of guanfacine against SIB was evaluated in 11 self-biting episodes among two rhesus macaques (Macaca mulatta) and one baboon (Papio cynocephalus anubis). Affected animals were given guanfacine IM or PO at 0.5 mg/kg of body weight twice daily (rhesus) or 0.3 mg/kg (baboon) for 5 to 10 days, followed by gradual reduction of the dose to 0.25 mg/kg (rhesus) or 0.15 mg/kg (baboon) once daily over an average of 33 days.
The 0.5 mg/kg twice daily regimen of guanfacine halted all self-biting, whereas reducing the dose to 0.25 mg/kg given twice daily or 0.5 mg/kg given once daily resulted in reversion to self-biting in four of the 11 episodes. Recurrence was controlled by returning to twice daily 0.5 mg/kg dosing for one aggressive episode, and resolved in the three milder episodes without dose or frequency being increased. Self-biting after discontinuation of therapy recurred six times over five years in case 1, three times over 1.5 years in case 2, and three times over one year in case 3. Clinical assessment suggested that guanfacine therapy decreased agitation without overt side effects associated with alpha2-agonists, such as profound sedation.
The mechanism for guanfacine inhibition of self-biting is unclear, but could result from strengthening of prefrontal cortex inhibitory functions. Guanfacine therapy provides an effective psychological stabilizing tool that alleviates self-biting, and provides time to assess and address external stressors and triggers.
自我伤害行为(SIB)影响0.8%至10%单独圈养的非人灵长类动物,对它们的健康和福祉构成重大威胁。SIB涉及多种神经递质以及对外部应激源反应的复杂变化,使病例管理变得复杂。使用胍法辛(一种α2A肾上腺素能受体激动剂)调节肾上腺素能系统被评估为一种治疗SIB的新策略。
在两只恒河猴(猕猴属)和一只狒狒(埃及狒狒)的11次自我咬伤事件中评估了胍法辛对SIB的疗效。受影响的动物以0.5毫克/千克体重的剂量每日两次(恒河猴)或0.3毫克/千克(狒狒)肌内注射或口服胍法辛,持续5至10天,随后在平均33天内逐渐将剂量减至0.25毫克/千克(恒河猴)或0.15毫克/千克(狒狒)每日一次。
胍法辛每日两次0.5毫克/千克的方案停止了所有自我咬伤行为,而将剂量减至每日两次0.25毫克/千克或每日一次0.5毫克/千克导致11次事件中的4次恢复自我咬伤。在一次攻击事件中,通过恢复每日两次0.5毫克/千克的给药控制了复发,在三次较轻的事件中,在未增加剂量或频率的情况下得以解决。病例1在停药后五年内自我咬伤复发六次,病例2在1.5年内复发三次,病例3在一年内复发三次。临床评估表明,胍法辛治疗减少了躁动,没有出现与α2激动剂相关的明显副作用,如深度镇静。
胍法辛抑制自我咬伤的机制尚不清楚,但可能是由于前额叶皮质抑制功能增强所致。胍法辛治疗提供了一种有效的心理稳定工具,可减轻自我咬伤,并为评估和应对外部应激源及触发因素提供时间。