Kempf Doty J, Baker Kate C, Gilbert Margaret H, Blanchard James L, Dean Reginald L, Deaver Daniel R, Bohm Rudolf P
Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana, USA.
Comp Med. 2012 Jun;62(3):209-17.
Self-injurious behavior (SIB) is a spontaneous behavior that threatens the health and wellbeing of multiple species. In humans, the opioid antagonist naltrexone hydrochloride has been used successfully to modulate the endogenous opioid system and reduce the occurrence of SIB. This study is the first to assess the efficacy of extended-release naltrexone in the pharmacologic treatment of SIB in rhesus macaques (Macaca mulatta). In an acute pharmacokinetic study of 4 macaques, we determined the mean naltrexone plasma concentration was maintained above the therapeutic level (2 ng/mL) after administration of a single dose (20 mg/kg) of 28-d extended-release naltrexone throughout the release period. For a subsequent treatment study, we selected 8 singly housed macaques known to engage in SIB. The study comprised a 4-wk baseline phase; an 8-wk treatment phase, during which each macaque received 2 doses of extended-release naltrexone 28 d apart; and a 4-wk posttreatment phase. Plasma samples were collected and analyzed weekly for naltrexone concentrations throughout the treatment and posttreatment phases. In addition, total of 6 h of video was analyzed per animal per phase of the study. Compared with baseline phases, both the frequency and the percentage of time spent displaying SIB decreased during the treatment phase, and the percentage of time remained decreased during the posttreatment phase. In contrast, extended-release naltrexone did not alter the expression of other abnormal, anxiety-related, or agonistic behaviors nor were levels of inactivity affected. The present study supports the use of naltrexone in the treatment of SIB in rhesus macaques.
自伤行为(SIB)是一种威胁多种物种健康和福祉的自发行为。在人类中,阿片类拮抗剂盐酸纳曲酮已成功用于调节内源性阿片系统并减少自伤行为的发生。本研究首次评估了长效纳曲酮在恒河猴(猕猴)自伤行为药物治疗中的疗效。在对4只猕猴进行的急性药代动力学研究中,我们确定在整个释放期给予单剂量(20mg/kg)的28天长效纳曲酮后,纳曲酮的平均血浆浓度在治疗水平(2ng/mL)以上维持。在随后的治疗研究中,我们选择了8只已知有自伤行为的单独饲养的猕猴。该研究包括一个4周的基线期;一个8周的治疗期,在此期间每只猕猴每隔28天接受2剂长效纳曲酮;以及一个4周的治疗后期。在整个治疗期和治疗后期,每周采集血浆样本并分析纳曲酮浓度。此外,在研究的每个阶段,每只动物总共分析6小时的视频。与基线期相比,在治疗期自伤行为的频率和发生时间百分比均下降,且在治疗后期发生时间百分比仍保持下降。相比之下,长效纳曲酮并未改变其他异常、焦虑相关或攻击性行为的表现,也未影响不活动水平。本研究支持使用纳曲酮治疗恒河猴的自伤行为。