Meltzer H Y, Maes M
Department of Psychiatry, Case Western Reserve University, School of Medicine, University Hospitals of Cleveland, OH 44106, USA.
Psychiatry Res. 1995 Sep 29;58(2):89-98. doi: 10.1016/0165-1781(95)02701-w.
Previous reports from this laboratory have shown that pindolol, a partial serotonin1A receptor agonist, inhibited prolactin, but not cortisol secretion induced by administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan or the direct-acting 5-HT2A/5HT2C receptor agonist MK-212. The findings suggest additive or interactive effects of 5-HT1A and 5-HT2A/5-HT2C receptors in modulating 5-HT-related prolactin, but not cortisol, responsivity. To examine further the role of 5-HT1A and 5-HT2A/5-HT2C receptors in prolactin and cortisol secretion in healthy men, the effects of meta-chlorophenylpiperazine (mCPP), a potent 5-HT receptor agonist, on the above hormones were studied in eight healthy men with and without pindolol pretreatment. It has previously been demonstrated that ketanserin, a 5-HT2A antagonist, and ritanserin, a 5-HT2A/5-HT2C antagonist, block the prolactin and attenuate the hypothalamic-pituitary-adrenal axis responses to mCPP in man or rodents. Administration of mCPP induced a significant increase in plasma concentrations of prolactin and cortisol. The mCPP-induced prolactin concentrations were significantly blocked by pretreatment with pindolol, whereas mCPP-stimulated cortisol levels were not diminished by pindolol pretreatment. Thus, mCPP-induced prolactin secretion appears to require the availability of both 5-HT2C and 5-HT1A receptor activation, since blockade of either of these receptors may diminish the mCPP-induced prolactin response. Cortisol secretion stimulated by mCPP may occur following 5-HT2C receptor stimulation in the presence of 5-HT1A receptor blockade.
本实验室之前的报告表明，吲哚洛尔作为一种部分血清素1A受体激动剂，可抑制催乳素分泌，但不能抑制由血清素（5-羟色胺，5-HT）前体L-5-羟色氨酸或直接作用的5-HT2A/5-HT2C受体激动剂MK-212诱导的皮质醇分泌。这些发现提示5-HT1A和5-HT2A/5-HT2C受体在调节5-HT相关的催乳素反应性方面具有相加或协同作用，但对皮质醇反应性无此作用。为了进一步研究5-HT1A和5-HT2A/5-HT2C受体在健康男性催乳素和皮质醇分泌中的作用，在8名健康男性中研究了强效5-HT受体激动剂间氯苯哌嗪（mCPP）对上述激素的影响，这些男性部分接受了吲哚洛尔预处理，部分未接受。此前已有研究表明，5-HT2A拮抗剂酮色林和5-HT2A/5-HT2C拮抗剂利坦色林可阻断人类或啮齿动物体内的催乳素分泌，并减弱下丘脑-垂体-肾上腺轴对mCPP的反应。给予mCPP可使血浆催乳素和皮质醇浓度显著升高。吲哚洛尔预处理可显著阻断mCPP诱导的催乳素浓度升高，而吲哚洛尔预处理并未降低mCPP刺激的皮质醇水平。因此，mCPP诱导的催乳素分泌似乎需要5-HT2C和5-HT1A受体同时激活，因为阻断这两种受体中的任何一种都可能减弱mCPP诱导的催乳素反应。在5-HT1A受体被阻断的情况下，mCPP刺激的皮质醇分泌可能是在5-HT2C受体被刺激后发生的。
