Deupree Jean D, Burke William J, Bylund David B
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800 USA.
BMC Pharmacol. 2008 Oct 2;8:17. doi: 10.1186/1471-2210-8-17.
The effects of acute and repeated treatment with desipramine on the functional response of alpha2-adrenoceptors were tested in adult and 13-day old rats. The functional response measured was hypothermia that was induced by brimonidine, an alpha2-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 alpha2-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 alpha2-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 alpha2-adrenoceptors with and without pretreatment with the antidepressant desipramine. In the absence of desipramine pretreatment, the alpha2-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 alpha2-agonist-induced hypothermic effect following repeated injections of desipramine that is seen in adult rats is not seen in juvenile rats.
在成年大鼠和13日龄大鼠中测试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。所测量的功能反应是由α2-肾上腺素能受体激动剂溴莫尼定诱导的体温过低。比较了13日龄和成年（65 - 75日龄）雄性大鼠单次或每日两次注射4次地昔帕明预处理后溴莫尼定诱导的体温过低程度的变化。
单独使用溴莫尼定时，幼年大鼠的直肠温度降低幅度大于成年大鼠，并且在两组大鼠中，这种反应均被选择性α2-肾上腺素能受体拮抗剂RX821002剂量依赖性地阻断。在无溴莫尼定的情况下，单次给予地昔帕明可使成年大鼠的直肠温度降低，但对幼年大鼠无此作用。地昔帕明治疗4天（每日两次，每次10mg/kg）后，成年大鼠对这种体温过低效应产生了耐受性。成年大鼠重复给予地昔帕明还导致在最后一剂后24小时溴莫尼定诱导的体温过低效应增强，此时超过90%的地昔帕明及其代谢产物去甲基地昔帕明已从脑中清除，但在最后一剂后14、48或96小时未出现这种情况。在幼年大鼠中，重复注射地昔帕明（每日两次，每次3mg/kg，共4天），在最后一剂地昔帕明后14、24、63和96小时给予溴莫尼定，对α2-激动剂诱导的体温过低没有影响。
结果表明，幼年大鼠与成年大鼠对α2-肾上腺素能受体激动剂刺激的反应不同，无论是否用地昔帕明进行预处理。在未用地昔帕明预处理的情况下，幼年大鼠中α2-肾上腺素能受体诱导的体温过低效应大于成年大鼠。在无激动剂的情况下，急性注射地昔帕明可使成年大鼠体温过低，但对幼年大鼠无此作用。此外，成年大鼠重复注射地昔帕明后出现的α2-激动剂诱导的体温过低效应增强在幼年大鼠中未观察到。
