Darmani N A, Ahmad B
Department of Pharmacology, Kirksville College of Osteopathic Medicine, Kirksville, Missouri, USA.
J Pharmacol Exp Ther. 1999 Jan;288(1):247-53.
Activation of 5-hydroxytryptamine1A (5-HT1A) receptors in rats produces hypothermia and a number of behaviors [hindleg abduction (HLA), lateral head-weaving (LHW), forepaw treading (FPT), flat body posture (FBP), rollover (RO), tremor (T), and straub tail (ST)] known collectively as the serotonin syndrome (SS). Stimulation of 5-HT2A receptors produces wet-dog shakes (WDS), whereas 5-HT2C sites induce back muscle contraction (BMC). We investigated the functional ontogeny of the cited receptors in rat pups on postnatal days (PD) 7, 14, 18, 22, 28, 35, 60, and 120 by using (1) the 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin (0, 1.25, and 5 mg/kg) to induce the SS and hypothermia and (2) the 5-HT2A/C agonist (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (0, 0.5, and 4 mg/kg) to produce both WDS and BMC. The age of onset for most symptoms of SS [FBP, HLA, RO, and T] was the first week of life. They attained maximal intensities at ages 7 to 14 days, after which their maxima either reduced or dissipated to zero. Per contra, the onset of LHW and FPT required 14 to 18 days, and their maxima developed later. The onset of (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane-induced WDS occurred after PD 14, and by PD 18, it reached its maximal intensity, which persisted up to PD 60, after which it declined. The onset of BMC was evident on PD 28 and attained its maximal frequency at ages 90 to 120 days. The results show that different components of SS appear within 14 days of birth, but they mature differentially, whereas the hypothermic effect of 5-HT1A receptors remains relatively constant during aging. The times of onset and maturation of WDS were intermediate (between the second and third weeks of life), whereas BMC required 1 to 2 months for its appearance and maturation.
激活大鼠体内的5-羟色胺1A（5-HT1A）受体会导致体温过低以及一系列统称为血清素综合征（SS）的行为[后肢外展（HLA）、头部侧向摆动（LHW）、前爪踩踏（FPT）、扁平体位（FBP）、翻滚（RO）、震颤（T）和弓背尾（ST）]。刺激5-HT2A受体会产生湿狗样抖动（WDS），而刺激5-HT2C位点会引起背部肌肉收缩（BMC）。我们通过使用（1）5-HT1A激动剂8-羟基-2-二丙基氨基四氢萘（0、1.25和5 mg/kg）来诱导血清素综合征和体温过低，以及（2）5-HT2A/C激动剂（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（0、0.5和4 mg/kg）来产生WDS和BMC，研究了出生后第7、14、18、22、28、35、60和120天的大鼠幼崽中上述受体的功能发育情况。血清素综合征大多数症状[FBP、HLA、RO和T]的发病年龄在出生后的第一周。它们在7至14天时达到最大强度，之后其最大值要么降低要么消散至零。相反，LHW和FPT的发病需要14至18天，且它们的最大值出现得较晚。（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷诱导的WDS在出生后第14天之后开始出现，到出生后第18天达到最大强度，并持续到出生后第60天，之后下降。BMC在出生后第28天开始出现，在90至120天时达到最大频率。结果表明，血清素综合征的不同组成部分在出生后14天内出现，但它们的成熟过程存在差异，而5-HT1A受体的体温过低效应在衰老过程中保持相对稳定。WDS的发病和成熟时间处于中间阶段（出生后第二至三周之间），而BMC的出现和成熟需要1至2个月。
