Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration.
Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration.
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DOI：
10.1186/1471-2210-8-17
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发表时间：
2008-10-02
期刊：
影响因子：
--
通讯作者：
Bylund DB
中科院分区：
文献类型：
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作者：
Deupree JD;Burke WJ;Bylund DB
在成年和13日龄大鼠上观察了地昔帕明急性和重复给药对α2肾上腺素能受体功能反应的影响。测量的功能反应是由α2肾上腺素受体激动剂溴莫尼定诱导的体温过低。在13日龄和成年（65-75日龄）雄性大鼠中，比较了单次或4次每日两次注射地昔帕明预处理后溴莫尼定诱导的低温程度的变化。单独溴莫尼定降低幼年大鼠直肠温度的程度大于成年大鼠，在两组大鼠中，选择性α2-肾上腺素受体拮抗剂RX 821002可剂量依赖性地阻断这种反应。单次地昔帕明给药降低直肠温度在成年大鼠中，但在幼年大鼠中不存在溴莫尼定。成年大鼠在地昔帕明治疗4天（10 mg/kg，每日两次）后对这种低温效应产生耐受性。反复地昔帕明治疗成年大鼠也导致溴莫尼定诱导的低温效应的增强后24小时最后一次给药时，超过90%的地昔帕明及其代谢产物，去甲基地昔帕明，已清除大脑，但不是在14，48或96小时后最后一次给药。在幼年大鼠中，当在末次地昔帕明给药后14、24、63和96 h给予溴莫尼定时，重复注射地昔帕明（3 mg/kg，每日2次，持续4 d）对α2激动剂诱导的低温没有影响。结果表明，未成年大鼠对α2-肾上腺素能受体激动剂刺激的反应不同于成年大鼠，有和没有预处理的抗抑郁药地昔帕明。在无地昔帕明预处理的情况下，幼年大鼠的α2-肾上腺素受体诱导的低温效应大于成年大鼠。急性注射地昔帕明，在没有激动剂的情况下，在成年大鼠中产生了低温效应，但在幼年大鼠中没有。此外，在成年大鼠中观察到的反复注射地昔帕明后α2激动剂诱导的低温效应增加在幼年大鼠中未观察到。
The effects of acute and repeated treatment with desipramine on the functional response of α2-adrenoceptors were tested in adult and 13-day old rats. The functional response measured was hypothermia that was induced by brimonidine, an α2-adrenoceptor agonist. The change in the extent of the brimonidine-induced hypothermia following pretreatment with either single or 4 twice-daily injections of desipramine was compared in 13-day old and adult (65–75 days old) male rats. Brimonidine, alone, lowered rectal temperature to a greater extent in juvenile than in adult rats, and this response was dose-dependently blocked by the selective α2-adrenoceptor antagonist, RX821002, in both groups of rats. Single desipramine administration lowered rectal temperature in the absence of brimonidine in adult but not in juvenile rats. The adult rats developed tolerance to this hypothermic effect after 4 days of desipramine treatment (10 mg/kg twice daily). Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose. In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the α2-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine. The results suggest that juvenile rats response differently than adult rats to agonist stimulation of α2-adrenoceptors with and without pretreatment with the antidepressant desipramine. In the absence of desipramine pretreatment, the α2-adrenoceptor-induced hypothermic effect in juvenile rats is greater than in adult rats. Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats. In addition, the increased α2-agonist-induced hypothermic effect following repeated injections of desipramine that is seen in adult rats is not seen in juvenile rats.