Department of Cellular and Physiological Sciences, Neuroscience Program, University of British Columbia, Vancouver, Canada.
Int J Neuropsychopharmacol. 2022 Oct 25;25(10):863-876. doi: 10.1093/ijnp/pyac046.
Male and female rats were exposed to repeated restraint to determine how changes in serotonin (5-hydroxytryptamine; 5-HT) 1A receptors associate with stress hypothalamic-pituitary-adrenal (HPA) axis habituation.
In response to 2-hour episodes of restraint, repeated daily for 5 consecutive days, males and females displayed reliable declines in HPA output, indicated by diminished adrenocorticotropin and corticosterone secretory responses. Using the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) as a pharmacological challenge for inducing hypothermia and elevations in plasma corticosterone, males displayed sensitized hypothermal responses after repeated restraint, whereas corticosterone responses to 8-OH-DPAT were enhanced in both sexes following single or repeated exposure.
Only males showed elevations in 5-HT 1A receptor G-protein coupling responses in the dorsal raphe after repeated restraint, whereas only females showed an increase in 5-HT 1A receptor responses in the hippocampus following single or repeated exposure. G-protein coupling responses within both regions correlated positively with 5-HT 1A receptor binding capacity. Thus, despite expressing similar capacities for stress HPA axis habituation, males and females emerged from repeated restraint to show region-specific changes in 5-HT 1A receptor function that may be explained, at least in part, by changes in receptor availability.
Based on the hypothermal and corticosteroid responses to 8-OH-DPAT, the present data suggest that stress habituation is met by an increase in the sensitivity of presynaptic 5-HT 1A receptors in males and by an increase in the sensitivity of a population of postsynaptic receptors in both sexes.
雄性和雌性大鼠反复受到束缚，以确定 5-羟色胺（5-HT）1A 受体的变化如何与应激下丘脑-垂体-肾上腺（HPA）轴习惯化相关联。
在 2 小时的束缚期内，雄性和雌性大鼠每天重复 5 天，对重复的束缚有可靠的反应，表现为促肾上腺皮质激素和皮质酮分泌反应减弱。使用 5-HT 1A 受体激动剂 8-羟基-2-（二丙基氨基）四氢萘（8-OH-DPAT）作为诱导体温下降和血浆皮质酮升高的药理学挑战，雄性大鼠在反复束缚后表现出敏化的体温反应，而 8-OH-DPAT 对皮质酮的反应在单次或重复暴露后在两性中均增强。
只有雄性大鼠在反复束缚后在背缝核中显示 5-HT 1A 受体 G 蛋白偶联反应升高，而只有雌性大鼠在单次或重复暴露后在海马体中显示 5-HT 1A 受体反应增加。两个区域的 G 蛋白偶联反应与 5-HT 1A 受体结合能力呈正相关。因此，尽管表达了相似的应激 HPA 轴习惯化能力，雄性和雌性大鼠在反复束缚后表现出 5-HT 1A 受体功能的区域特异性变化，这些变化至少部分可以用受体可用性的变化来解释。
基于对 8-OH-DPAT 的体温和皮质酮反应，本数据表明，应激习惯化是通过增加雄性大鼠中 5-HT 1A 受体的突触前敏感性和两性中突触后受体的敏感性来实现的。
