Perret G, Schluger J H, Unterwald E M, Kreuter J, Ho A, Kreek M J
The Rockefeller University, New York, New York 10021, USA.
Synapse. 1998 Oct;30(2):166-71. doi: 10.1002/(SICI)1098-2396(199810)30:2<166::AID-SYN6>3.0.CO;2-A.
The effect of chronic cocaine exposure on the central serotonergic system in the rat was investigated using a selective 5-HT1A receptor agonist, [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), and a 5-HT2A receptor antagonist, [3H]ketanserin, as tritiated ligands in a quantitative autoradiography study. Rats were administered cocaine in a "binge" pattern, 15 mg/kg/injection, three times a day, at 1-h intervals for 14 days to mimic the pattern often seen in human cocaine addicts. A significant decrease in the binding of [3H]8-OH-DPAT was found in the ventromedial hypothalamus (P < 0.001) and the dorsal dentate gyrus (P < 0.01) in rats administered cocaine as compared with rats injected with saline. No significant difference in the binding of [3H]ketanserin was found in frontal, parietal, agranular insular, and piriform cortices, caudate-putamen, olfactory tubercle, nucleus accumbens, thalamus, septohippocampal nucleus, and claustrum. Several studies have shown that 5-HT1A receptor agonists have antidepressant properties. Other studies, in animal models, have shown that 5-HT1A receptor agonists stimulate the hypothalamic-pituitary-adrenal axis, which is of interest, since chronic activation of this axis has been related to anxiety and depression. Our data show that the 5-HT1A component of the serotonergic system is altered following chronic "binge" pattern cocaine administration in an animal model and may be related to changes in the HPA axis and behavior.
在一项定量放射自显影研究中，使用选择性5-HT1A受体激动剂[3H]8-羟基-2-（二-N-丙基氨基）四氢萘（8-OH-DPAT）和5-HT2A受体拮抗剂[3H]酮色林作为氚标记配体，研究了长期接触可卡因对大鼠中枢5-羟色胺能系统的影响。以“暴饮暴食”模式给大鼠注射可卡因，剂量为15mg/kg/次，每天3次，间隔1小时，持续14天，以模拟人类可卡因成瘾者常见的模式。与注射生理盐水的大鼠相比，给予可卡因的大鼠腹内侧下丘脑（P<0.001）和背侧齿状回（P<0.01）中[3H]8-OH-DPAT的结合显著降低。在额叶、顶叶、无颗粒岛叶和梨状皮质、尾状核-壳核、嗅结节、伏隔核、丘脑、隔海马核和屏状核中，[3H]酮色林的结合未发现显著差异。多项研究表明，5-HT1A受体激动剂具有抗抑郁特性。在动物模型中的其他研究表明，5-HT1A受体激动剂刺激下丘脑-垂体-肾上腺轴，这一点很有趣，因为该轴的慢性激活与焦虑和抑郁有关。我们的数据表明，在动物模型中，长期以“暴饮暴食”模式给予可卡因后，5-羟色胺能系统的5-HT1A成分发生改变，可能与下丘脑-垂体-肾上腺轴和行为的变化有关。
