Winslow J T, Insel T R
Laboratory of Clinical Science, National Institute of Mental Health, NIHAC, Poolesville, MD 20837.
Neuropsychopharmacology. 1990 Feb;3(1):51-9.
Rat pups emit a highly stereotyped and well-characterized distress call in the ultrasonic range when socially isolated. We compared the modulatory influence of catecholamines and indoleamines on rat pup ultrasonic calls using pharmacologic probes. Administration of low doses of monoamine reuptake inhibitors produced significant, selective changes in the calls emitted by isolated 10-day-old pups. Acute administration of clomipramine (CMI; relatively 5-HT specific) reduced the rate of calling at low doses (1.0 and 5.0 mg/kg [3.2 and 18.0 mmol/kg] SC) but had reduced efficacy at higher doses (10 and 20 mg/kg [32.0 and 63.7 mmol/kg] SC). Motor activity and rectal body temperature were unaffected at these doses. Similarly, low doses of other 5-HT-selective uptake inhibitors, such as paroxetine (1.0 mg/kg [3.1 mmol/kg] SC) and citalopram (1.0 mg/kg [3.09 mmol/kg] SC), virtually eliminated isolation calling. The effects of CMI were not antagonized by either naltrexone (0.1 mg/kg [0.28 mmol/kg] SC) or Ro 15-1788 (5.0 mg/kg [16.5 mmol/kg] SC). Desipramine (DMI; norepinephrine [NE] specific) significantly increased calling rates at all doses tested (1.0 to 10.0 mg/kg [3.8 to 75 mmol/kg] SC). These effects were associated with significant reductions in body temperature, but not motor activity. Similar increases in the rate of isolation calling, reduction in rectal body temperature, and an increase in motor activity were produced by low doses of mazindol (0.5 mg/kg [1.75 mmol/kg] SC) and nortriptyline (1.0 mg/kg [19 mmol/kg] SC). In an additional study, the chronic effects of CMI and desipramine were evaluated with treatment beginning within 24 hours after birth.(ABSTRACT TRUNCATED AT 250 WORDS)
幼鼠在社会隔离时会发出超声波范围内高度刻板且特征明确的痛苦叫声。我们使用药理学探针比较了儿茶酚胺和吲哚胺对幼鼠超声波叫声的调节影响。给予低剂量的单胺再摄取抑制剂会使隔离状态下的10日龄幼鼠发出的叫声产生显著的、选择性的变化。急性给予氯米帕明(CMI;相对特异性作用于5-羟色胺)在低剂量(1.0和5.0毫克/千克[3.2和18.0毫摩尔/千克]皮下注射)时会降低叫声频率,但在高剂量(10和20毫克/千克[32.0和63.7毫摩尔/千克]皮下注射)时效果减弱。这些剂量下运动活动和直肠体温未受影响。同样,低剂量的其他5-羟色胺选择性摄取抑制剂,如帕罗西汀(1.0毫克/千克[3.1毫摩尔/千克]皮下注射)和西酞普兰(1.0毫克/千克[3.09毫摩尔/千克]皮下注射),几乎消除了隔离叫声。CMI的作用既不被纳曲酮(0.1毫克/千克[0.28毫摩尔/千克]皮下注射)也不被Ro 15-1788(5.0毫克/千克[16.5毫摩尔/千克]皮下注射)拮抗。地昔帕明(DMI;特异性作用于去甲肾上腺素[NE])在所有测试剂量(1.0至10.0毫克/千克[3.8至75毫摩尔/千克]皮下注射)下均显著提高叫声频率。这些作用与体温显著降低有关,但与运动活动无关。低剂量的马吲哚(0.5毫克/千克[1.75毫摩尔/千克]皮下注射)和去甲替林(1.0毫克/千克[19毫摩尔/千克]皮下注射)也会产生类似的隔离叫声频率增加、直肠体温降低以及运动活动增加的情况。在另一项研究中,在出生后24小时内开始治疗,评估了CMI和地昔帕明的慢性影响。(摘要截短于250字)