Van de Kar L D, Li Q, Cabrera T M, Brownfield M S, Battaglia G
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, USA.
J Pharmacol Exp Ther. 1998 Jul;286(1):256-62.
In the present study, we examined denervation-induced changes in the sensitivity of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect to changes in the dose-dependent elevation in plasma hormones [adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin, prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of 5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93% reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone and prolactin levels were shifted to the left in rats treated with 5,7-DHT, whereas no significant difference in the ACTH dose-response curve was observed between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7-DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%) in plasma renin concentration but not in vasopressin levels in rats that received i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5-HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic serotonergic nerve terminals produces supersensitivity of some neuroendocrine responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5-HT1A receptors.
在本研究中，我们检测了去神经支配诱导的下丘脑突触后5-羟色胺1A（5-HT1A）受体功能敏感性的变化，该变化与5-HT1A激动剂8-羟基-2-（二丙基氨基）四氢萘（8-OH-DPAT）引起的血浆激素[促肾上腺皮质激素（ACTH）、皮质酮、催乳素、催产素、肾素和血管加压素]剂量依赖性升高的变化有关。在用递增剂量的8-OH-DPAT（0、10、50或200微克/千克皮下注射）激发前3周，大鼠接受脑室内（i.c.v.）注射5-羟色胺神经毒素5,7-二羟基色胺（5,7-DHT）或溶剂（0.1%抗坏血酸钠盐水溶液）。下丘脑[3H]帕罗西汀标记的5-羟色胺摄取位点减少93%，证实了5,7-DHT诱导的血清素能神经元破坏的有效性。接受i.c.v. 5,7-DHT注射的大鼠中，未观察到ACTH、皮质酮、催产素、催乳素、肾素和血管加压素的基础水平有变化。在用5,7-DHT处理的大鼠中，8-OH-DPAT诱导的血浆皮质酮和催乳素水平升高的剂量反应曲线向左移动，而在用溶剂处理的大鼠和用5,7-DHT处理的大鼠之间，ACTH剂量反应曲线未观察到显著差异。相反，在用5,7-DHT处理的大鼠中，对8-OH-DPAT的最大催产素反应减弱。5,7-DHT诱导的催产素合成下降可以解释这一现象。尽管8-OH-DPAT在接受溶剂处理的大鼠中未增加血浆肾素或血管加压素水平，但8-OH-DPAT在接受i.c.v.注射5,7-DHT的大鼠中使血浆肾素浓度升高（75%），但未使血管加压素水平升高。下丘脑[3H]8-OH-DPAT标记的5-HT1A受体未观察到变化。总之，下丘脑血清素能神经末梢的去神经支配导致一些神经内分泌反应对8-OH-DPAT产生超敏反应，这与下丘脑5-HT1A受体密度的变化无关。
