Winslow J T, Insel T R
National Institute of Mental Health, Poolesville, Maryland.
J Pharmacol Exp Ther. 1990 Jul;254(1):212-20.
3,4-Methylenedioxymethamphetamine (MDMA) has previously been shown to destroy serotonin terminals in the rat brain. Despite profound and prolonged loss of serotonin innervation, long-term behavioral effects of MDMA have not previously been reported. In this study, we monitored the short- and long-term effects of MDMA administration on the ultrasonic isolation call of the rat pup. At 30 to 60 min after a single dose of MDMA (0.5-10.0 mg/kg), isolation calls decreased as much as 90%, with a rebound increase in calling noted 10 to 25 h following administration of the highest dose. Repeated administration of 10 mg/kg MDMA (once or twice daily on postnatal days 1-4) resulted in a lasting, dose-dependent decrease in ultrasonic vocalization monitored on days 6, 9, 12 and 15. Concurrent measures of locomotor behavior, geotaxis and weight gain were not altered subsequent to repeated MDMA treatment. Both serotonin content and serotonin terminals (assessed by [3H]paroxetine binding) in cortex were reduced by repeated MDMA treatment, whereas concentrations of catecholamines and their metabolites were unaltered. Repeated prenatal MDMA exposure did not affect postnatal rates of calling or the biochemical markers of serotonin in cortex. Pups lesioned with MDMA postnatally showed not only long-term behavioral and biochemical changes but also altered responsiveness to the serotonin 1B agonist 1-[3-(trifluromethyl)phenyl]piperazine. Taken together, these studies indicate that serotonergic lesions in a sensitive phase of development can have long-term selective effects on the rat pup ultrasonic isolation call, a behavior critical for mother-infant affiliation.
3,4-亚甲基二氧甲基苯丙胺（摇头丸）先前已被证明会破坏大鼠大脑中的血清素终端。尽管血清素神经支配出现了严重且持久的丧失，但摇头丸的长期行为影响此前尚未见报道。在本研究中，我们监测了给予摇头丸对大鼠幼崽超声隔离叫声的短期和长期影响。单次给予摇头丸（0.5 - 10.0毫克/千克）后30至60分钟，隔离叫声减少多达90%，在给予最高剂量后10至25小时观察到叫声出现反弹增加。重复给予10毫克/千克摇头丸（在出生后第1 - 4天每天一次或两次）导致在第6、9、12和15天监测到的超声发声持续出现剂量依赖性降低。重复给予摇头丸治疗后，同时测量的运动行为、趋地性和体重增加并未改变。重复给予摇头丸治疗会降低皮层中的血清素含量和血清素终端（通过[3H]帕罗西汀结合评估），而儿茶酚胺及其代谢物的浓度未改变。产前重复暴露于摇头丸并未影响出生后的叫声频率或皮层中血清素的生化标志物。出生后用摇头丸损伤的幼崽不仅出现了长期行为和生化变化，而且对血清素1B激动剂1-[3-（三氟甲基）苯基]哌嗪的反应性也发生了改变。综上所述，这些研究表明，在发育的敏感阶段发生的血清素能损伤可对大鼠幼崽的超声隔离叫声产生长期的选择性影响，这种行为对母婴依恋至关重要。
