Abstract

Post-traumatic stress disorder (PTSD) is often comorbid with cocaine use disorder (CUD), but little is known about hypothalamic-pituitary-adrenal (HPA) axis function in PTSD + CUD. Here we review the clinical and pre-clinical literature of PTSD and CUD with the goal of generating hypotheses about HPA axis activity in comorbid PTSD + CUD. Low glucocorticoid (CORT) levels immediately after trauma exposure are associated with PTSD. CORT administered within 12 h of trauma exposure reduces later PTSD symptoms. Weeks-years after trauma, meta-analyses find lower CORT levels in patients with PTSD relative to never-traumatized controls; the same is found in a pre-clinical model of PTSD. In rodents, reduced basal CORT levels are consistently found after chronic cocaine self-administration. Conversely, increased CORT levels are found in CUD patients during the first 2 weeks of cocaine abstinence. There is evidence for CORT hyper-suppression after dexamethasone, high glucocorticoid receptor (GR) number pre-trauma, and increased GR translocation to the nucleus in PTSD. Hyper-suppression of HPA axis activity after dexamethasone suggests that PTSD individuals may have increased anterior pituitary GR. Given evidence for decreased anterior pituitary GR in rats that self-administer cocaine, PTSD + CUD individuals may have normal GR density and low basal CORT levels during late abstinence. Future studies should aim to reconcile the differences in pre-clinical and clinical basal CORT levels during cocaine and assess HPA axis function in both rodent models of CUD that consider stress-susceptibility and in PTSD + CUD individuals. Although additional studies are necessary, individuals with PTSD + CUD may benefit from behavioral and psychopharmacological treatments to normalize HPA axis activity.

• LAY SUMMARY

• Post-traumatic stress disorder (PTSD) is often comorbid with cocaine use disorder (CUD), but little is known about the hypothalamic-pituitary-adrenal (HPA) axis function in PTSD + CUD. The current review provides a synthesis of available clinical and pre-clinical data on PTSD and CUD with the goal of generating hypotheses about HPA axis activity in comorbid PTSD + CUD. While this review finds ample evidence supporting aberrant HPA axis activity in both PTSD and CUD, it suggests that more research is needed to understand the unique changes HPA axis activity in PTSD + CUD, as well as the bidirectional relationship between stress-susceptibility and motivation to seek cocaine.

摘要

创伤后应激障碍（PTSD）通常与可卡因使用障碍（CUD）并存，但对PTSD + CUD中的下丘脑-垂体-肾上腺（HPA）轴功能了解甚少。在这里，我们综述了PTSD和CUD的临床和临床前文献，目的是就PTSD + CUD合并症中的HPA轴活动产生假设。创伤暴露后立即出现低糖皮质激素（CORT）水平与PTSD相关。创伤暴露后12小时内施用CORT可减轻以后的PTSD症状。创伤后数周，荟萃分析发现PTSD患者的CORT水平要低于从未接受过创伤的对照组。在PTSD的临床前模型中也发现了同样的情况。在啮齿类动物中，长期服用可卡因后，始终可以发现降低的基础CORT水平。反过来，在可卡因戒断的前两周，CUD患者发现CORT水平升高。有证据表明，地塞米松，创伤前高糖皮质激素受体（GR）数量高，以及GRSD向PTSD核移位的CORT过度抑制。地塞米松后HPA轴活动的过度抑制表明PTSD患者的垂体前叶GR可能增加。自给自足可卡因的大鼠垂体前叶GR降低的证据表明，PTSD + CUD个体在戒酒后期可能具有正常的GR密度和较低的基础CORT水平。未来的研究应旨在调和可卡因期间临床前和临床基础CORT水平的差异，并评估考虑了压力敏感性的CUD啮齿动物模型和PTSD + CUD个体的HPA轴功能。

• 图层摘要

• 创伤后应激障碍（PTSD）通常与可卡因使用障碍（CUD）并存，但对PTSD + CUD中的下丘脑-垂体-肾上腺（HPA）轴功能了解甚少。本综述提供了有关PTSD和CUD的可用临床和临床前数据的综合，目的是生成关于合并PTSD + CUD中HPA轴活动的假设。虽然本综述找到了足够的证据支持PTSD和CUD中HPA轴活动异常，但它表明需要更多的研究来了解PTSD + CUD中HPA轴活动的独特变化，以及应激易感性和动机之间的双向关系。寻求可卡因。