Serotonergic function in cocaine addicts: Prolactin responses to sequential D,L-fenfluramine challenges
Serotonergic function in cocaine addicts: Prolactin responses to sequential D,L-fenfluramine challenges
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DOI：
10.1016/s0006-3223(98)00268-6
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发表时间：
1999-05-15
影响因子：
10.6
通讯作者：
McKernin, C
中科院分区：
文献类型：
--
作者：
Buydens-Branchey, L;Branchey, M;McKernin, C
背景：临床前研究表明，可卡因会改变血清素能功能，但我们对人类滥用可卡因导致的血清素能改变的了解仍然不全面。因此，我们通过使用 5-羟色胺释放剂和再摄取抑制剂 D,L-芬氟拉明 (FEN) 进行神经内分泌挑战来评估可卡因成瘾者和对照受试者的中枢 5-羟色胺能反应性。 方法：在 25 名住院男性可卡因成瘾者和 13 名健康男性受试者中研究了口服 60 mg FEN 和安慰剂后的血浆催乳素水平，对照受试者接受了一组 FEN/安慰剂挑战，可卡因成瘾者在停止可卡因后的第一周和第三周内面临两组挑战，根据父亲是否有药物滥用史（FH+）和不存在（FH-），将患者分为两个亚组。进行了以下比较： 1) 对照受试者与整个患者组以及患者亚组； 2) 整个患者组和患者亚组对第一个和第二个挑战的反应； 3) FH+ 与 FH- 患者的早期反应以及 FH+ 与 FH- 患者的晚期反应 结果：随着可卡因停药时间的增加，整个患者组中催乳素对 FEN 的反应显着增加。与 FH- 患者和对照受试者相比，FH+ 患者的早期反应明显减弱。与 FH- 患者相比，FH+ 患者的反应出现更明显的反弹。因此，FH+ 和 FH- 患者以及 FH+ 患者和对照受试者的晚期反应的比较变得不显着。结论：可卡因的使用似乎对介导人类催乳素释放的血清素能机制有影响。在本研究中，这种效应在有父亲酗酒或药物滥用史的患者亚组中更为明显。可卡因停药几天内观察到的催乳素反应更加减弱，随后两周后这种反应出现更大反弹，可能表明这些患者对可卡因破坏性作用的脆弱性增加，Biol Psychiatry 1999;45:1300-1306 (C) 1999 Society of Biological Psychiatry。
Background: Preclinical studies have shown that cocaine produces alterations in serotonergic function but our knowledge of the serotonergic alterations due to cocaine abuse in humans is still fragmentary. We therefore assessed the central serotonergic responsivity of cocaine addicts and control subjects by neuroendocrine challenges with the serotonin releaser and reuptake inhibitor D,L-fenfluramine (FEN).Methods: Plasma prolactin levels following a 60 mg oral dose of FEN and placebo were studied in 25 hospitalized male cocaine addicts and 13 healthy male subjects, Control subjects underwent one set of FEN/placebo challenges and cocaine addicts two sets of challenges, during the first and third weeks following cocaine discontinuation, Patients were divided into two subgroups as a function of presence (FH+) and absence (FH-) of a paternal history of substance abuse. The following comparisons were made: 1) Control subjects versus entire patient group and versus patient subgroups; 2) entire patient group and patient subgroups responses to first versus second challenges; 3) FH+ versus FH- patients' early responses and FH+ versus FH- patients' late responses,Results: The prolactin responses to FEN increased significantly in the entire patient group as time following cocaine discontinuation increased. The FH+ patients had significantly blunted early responses by comparison with FH- patients and control subjects, There was a more pronounced rebound of the responses of FH+ patients by comparison with those of FH- patients. As a result, comparisons of the late responses of FH+ and FH- patients and of FH+ patients and control subjects became nonsignificant.Conclusions: Cocaine use appears to have an effect on the serotonergic mechanisms mediating prolactin release in humans. In the present study, this effect was more pronounced in a subgroup of patients with a paternal history of alcoholism or drug abuse. The greater blunting of the prolactin response observed within days of cocaine discontinuation followed by a greater rebound of this response 2 weeks later could indicate an increased vulnerability to the disruptive effects of cocaine in these patients, Biol Psychiatry 1999;45:1300-1306 (C) 1999 Society of Biological Psychiatry.