Hagen Eunice, Shprung Dana, Minakova Elena, Washington James, Kumar Udaya, Shin Don, Sankar Raman, Mazarati Andrey
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1752, USA.
Neurotherapeutics. 2015 Jul;12(3):657-66. doi: 10.1007/s13311-015-0357-7.
Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sulfonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.
自闭症是一种发育障碍,其特征在于社交和沟通能力受损,以及存在受限和重复行为。自闭症的发病率高于早期估计,并且治疗效果有限且成本高昂。有限的临床和实验证据表明,自闭症患者可能从电休克疗法(ECT)中获益。我们研究了ECT在BTBR T + tf/j小鼠中的治疗潜力,该小鼠代表了一种经过验证的自闭症模型。在7天内每天两次给予一系列13次电休克刺激(ECS),当在最后一次ECS后24小时对动物进行测试时,可逆转核心自闭症样行为异常——社交能力受损、对新事物的社交反应以及重复行为。ECT的效果可持续长达2周。单次ECS或一系列6次ECS均未改变动物的行为。向侧脑室慢性注入一种选择性催产素受体阻滞剂(2S)-2-氨基-N-[(1S,2S,4R)-7,7-二甲基-1-[[[4-(2-甲基苯基)-1-哌嗪基]磺酰基]甲基]双环[2.2.1]庚-2-基]-4-(甲基磺酰基)丁酰胺盐酸盐,消除了ECT诱导的社交能力改善,并减轻了对新事物社交反应的改善,但不影响ECT诱导的重复行为逆转。这些原理验证实验表明,ECT确实可能对自闭症治疗有用,并且其治疗效果可能部分由中枢催产素信号介导。