Li Q, Brownfield M S, Levy A D, Battaglia G, Cabrera T M, Van de Kar L D
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL.
Biol Psychiatry. 1994 Sep 1;36(5):300-8. doi: 10.1016/0006-3223(94)90627-0.
The present study had two objectives: (1) to provide information on neuroendocrine challenge tests that can lead to diagnostic tests in humans; and (2) to confirm our previous observation that chronic fluoxetine selectively inhibits serotonin (5-HT1A) receptor function. We determined the effect of chronic fluoxetine and desipramine (DMI) on the hormone response to ipsapirone, a 5-HT1A agonist and a potential anxiolytic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, and prolactin, but not renin or vasopressin concentrations in plasma. Chronic fluoxetine, but not DMI, significantly inhibited the effect of ipsapirone on plasma oxytocin, ACTH and corticosterone concentrations. Chronic fluoxetine also reduced the Bmax for 3H-8-hydroxy-2-(dipropylamino) tetralin (3H-8-OH-DPAT) labelled 5-HT1A receptors in the midbrain. Neither antidepressant altered the density or affinity of 5-HT uptake sites. In conclusion, the present results confirm our previous results using 8-OH-DPAT as a challenge, and suggest that chronic 5-HT uptake inhibition results in adaptive changes leading to decreased function of the 5-HT1A receptor system. Finally, because ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients.
（1）提供有关可用于人类诊断测试的神经内分泌激发试验的信息；（2）证实我们之前的观察结果，即慢性氟西汀选择性抑制5-羟色胺（5-HT1A）受体功能。我们确定了慢性氟西汀和去甲丙咪嗪（DMI）对伊沙匹隆（一种5-HT1A激动剂和潜在的抗焦虑药物）激素反应的影响。伊沙匹隆可提高血浆中催产素、促肾上腺皮质激素（ACTH）、皮质酮和催乳素的水平，但不会提高肾素或血管加压素的浓度。慢性氟西汀而非DMI能显著抑制伊沙匹隆对血浆催产素、ACTH和皮质酮浓度的影响。慢性氟西汀还降低了中脑3H-8-羟基-2-（二丙基氨基）四氢萘（3H-8-OH-DPAT）标记的5-HT1A受体的Bmax。两种抗抑郁药均未改变5-羟色胺摄取位点的密度或亲和力。总之，目前的结果证实了我们之前使用8-OH-DPAT作为激发剂的结果，并表明慢性5-羟色胺摄取抑制会导致适应性变化，从而导致5-HT1A受体系统功能下降。最后，由于伊沙匹隆可用于人类，它可能可用于评估抑郁症患者的5-HT1A受体功能。
