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阿扑吗啡的神经内分泌效应:反应模式的特征及其在精神分裂症研究中的应用

Neuroendocrine effects of apomorphine: characterization of response patterns and application to schizophrenia research.

作者信息

Rotrosen J, Angrist B, Gershon S, Paquin J, Branchey L, Oleshansky M, Halpern F, Sachar E J

出版信息

Br J Psychiatry. 1979 Nov;135:444-56. doi: 10.1192/bjp.135.5.444.

Abstract

Apomorphine, a direct-acting dopamine agonist, stimulates release of growth hormone (hGH) and suppresses release of prolactin (PRL) from the anterior pituitary. Previous studies comparing the magnitude of these responses in schizophrenics and controls suggest that many acute (and some chronic) schizophrenics have exaggerated hGH responses; many chronic schizophrenics (and patients with tardive dyskinesia) have blunted hGH responses to apomorphine, and possibly blunted PRL responses. The present studies extend and confirm these findings in chronic schizophrenics; in addition, several studies were undertaken to further characterize these apomorphine-induced endocrine responses. Studies in which apomorphine was given on 2 or 3 separate occasions to each of five subjects indicate that the hGH response is a highly reproducible individual index, but PRL suppression is a less satisfactory measure. hGH responses to apomorphine were consistently antagonized by pretreatment with haloperidol, supporting the concept that the hGH-releasing effect of apomorphine is mediated by its action on dopamine receptors. Cyproheptadine pretreatment was associated with erratic increases or decreases in the hGH response to apomorphine, but did not alter PRL levels or apomorphine-induced PRL suppression. The relationship of these findings to biological hypotheses of schizophrenia and to neuroleptic-induced receptor changes is discussed.

摘要

阿扑吗啡是一种直接作用的多巴胺激动剂,可刺激生长激素(hGH)的释放,并抑制垂体前叶催乳素(PRL)的释放。先前比较精神分裂症患者和对照组这些反应程度的研究表明,许多急性(以及一些慢性)精神分裂症患者的hGH反应过度;许多慢性精神分裂症患者(以及迟发性运动障碍患者)对阿扑吗啡的hGH反应迟钝,并且PRL反应可能也迟钝。本研究扩展并证实了慢性精神分裂症患者的这些发现;此外,还进行了几项研究以进一步描述这些阿扑吗啡诱导的内分泌反应。对五名受试者每人在2或3个不同时间给予阿扑吗啡的研究表明,hGH反应是一个高度可重复的个体指标,但PRL抑制是一个不太理想的指标。预先用氟哌啶醇处理可始终拮抗阿扑吗啡引起的hGH反应,这支持了阿扑吗啡释放hGH的作用是通过其对多巴胺受体的作用介导的这一概念。预先用赛庚啶处理与阿扑吗啡引起的hGH反应的不稳定增加或减少有关,但不改变PRL水平或阿扑吗啡诱导的PRL抑制。讨论了这些发现与精神分裂症生物学假说以及抗精神病药物诱导的受体变化的关系。

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