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动情周期和眶额皮质在雌性大鼠戒断 15 天后寻找羟考酮中的作用。

Role of oestrous cycle and orbitofrontal cortex in oxycodone seeking after 15-day abstinence in female rats.

机构信息

Department of Psychology, University of Maryland College Park, College Park, Maryland, USA.

出版信息

Addict Biol. 2023 Oct;28(10):e13325. doi: 10.1111/adb.13325.

Abstract

Relapse to oxycodone seeking progressively increases after abstinence in rats, a phenomenon termed incubation of oxycodone craving. We have previously shown that the orbitofrontal cortex (OFC) plays a critical role in incubation of oxycodone craving in male rats. Here, we examined the effect of oestrous cycle on incubated oxycodone seeking in female rats, and whether the critical role of OFC in incubated oxycodone seeking generalizes to female rats. We first assessed oxycodone self-administration and incubated oxycodone seeking on abstinence day 15 across the oestrous cycle. Next, we determined the effect of chemogenetic inactivation of OFC by JHU37160 (J60), a novel agonist for Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), on incubated oxycodone seeking on abstinence day 15. Finally, we determined the effect of J60 alone on incubated oxycodone seeking on abstinence day 15. We found no difference in oxycodone intake across oestrus, pro-oestrus, and metoestrus stages during oxycodone self-administration training. Incubated oxycodone seeking was also similar between nonoestrus and oestrus female rats. Moreover, chemogenetic inactivation of OFC by J60 decreased incubated oxycodone seeking on abstinence day 15, while J60 alone had no effect on incubated oxycodone seeking in no-DREADD control rats. Taken together, results here show that the oestrous cycle has no effect on oxycodone intake and incubated oxycodone seeking in female rats under our experimental conditions. Furthermore, consistent with our previous findings in male rats, results here show that OFC also plays a critical role in incubated oxycodone seeking in female rats.

摘要

在大鼠中,戒断后对羟考酮觅药的反弹逐渐增加,这种现象称为羟考酮觅药的潜伏期。我们之前已经表明,眶额皮质(OFC)在雄性大鼠中羟考酮觅药潜伏期中起着关键作用。在这里,我们检查了发情周期对雌性大鼠中潜伏期羟考酮觅药的影响,以及 OFC 在潜伏期羟考酮觅药中的关键作用是否普遍适用于雌性大鼠。我们首先在发情周期内评估了羟考酮自我给药和潜伏期羟考酮觅药在戒断第 15 天的情况。接下来,我们通过新型 Designer Receptors Exclusively Activated by Designer Drugs(DREADDs)激动剂 JHU37160(J60)确定 OFC 的化学遗传失活对戒断第 15 天潜伏期羟考酮觅药的影响。最后,我们单独确定了 J60 在戒断第 15 天对潜伏期羟考酮觅药的影响。在羟考酮自我给药训练过程中,我们没有发现发情、发情前期和动情期阶段的羟考酮摄入量有差异。非发情期和发情期雌性大鼠的潜伏期羟考酮觅药也相似。此外,J60 通过化学遗传失活 OFC 可减少戒断第 15 天的潜伏期羟考酮觅药,而 J60 本身对无 DREADD 对照大鼠的潜伏期羟考酮觅药没有影响。总的来说,这些结果表明,在我们的实验条件下,发情周期对雌性大鼠的羟考酮摄入和潜伏期羟考酮觅药没有影响。此外,与我们之前在雄性大鼠中的发现一致,这些结果表明,OFC 在雌性大鼠中潜伏期羟考酮觅药中也起着关键作用。

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