Gartside S E, Ellis P M, Sharp T, Cowen P J
University Department of Psychiatry, Littlemore Hospital, Oxford, UK.
Eur J Pharmacol. 1992 Oct 6;221(1):27-33. doi: 10.1016/0014-2999(92)90768-y.
The 5-HT receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) produced dose-dependent increases in plasma adrenocorticotropin (ACTH) in the male rat by activation of 5-HT1A and 5-HT2 receptors respectively. The ACTH response to DOI was enhanced by repeated administration of electroconvulsive shock (five over 10 days) but abolished by the tricyclic antidepressant, amitriptyline (20 mg/kg for 14 days). In contrast 21 days lithium treatment failed to alter DOI-induced ACTH release. Neither repeated electroconvulsive shock, nor amitriptyline, nor lithium altered the ACTH response to 8-OH-DPAT. These data are consistent with results from ligand binding and behavioural studies which suggest that the sensitivity of brain 5-HT2 receptors is increased by repeated electroconvulsive shock but attenuated by tricyclic antidepressant treatment. In contrast, our data suggest that the antidepressant treatments studied do not alter the sensitivity of the 5-HT1A receptors involved in ACTH release.
5-羟色胺（5-HT）受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）和1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI），分别通过激活5-HT1A和5-HT2受体，使雄性大鼠血浆促肾上腺皮质激素（ACTH）呈剂量依赖性增加。反复给予电惊厥休克（10天内5次）可增强对DOI的ACTH反应，但三环类抗抑郁药阿米替林（20mg/kg，共14天）可消除该反应。相比之下，锂盐治疗21天未能改变DOI诱导的ACTH释放。反复电惊厥休克、阿米替林或锂盐均未改变对8-OH-DPAT的ACTH反应。这些数据与配体结合和行为学研究结果一致，表明反复电惊厥休克可增加脑5-HT2受体的敏感性，但三环类抗抑郁药治疗可使其减弱。相比之下，我们的数据表明，所研究的抗抑郁药治疗并未改变参与ACTH释放的5-HT1A受体的敏感性。
