BACKGROUND Cocaine withdrawal activates stress systems. Females are more vulnerable to relapse to cocaine use and more sensitive to withdrawal-induced negative affect. Delta opioid receptors modulate anxiety-like behavior during cocaine withdrawal in rats. This study measured the time course of gene regulation of one of the main stress peptides, corticotropin-releasing factor (CRF), and its type 1 receptor in male and female rats as well as the ability of the delta opioid receptor agonist SNC80 to normalize cocaine withdrawal-induced changes in CRF mRNA. METHODS Rats were injected with cocaine or saline 3 times daily for 14 days. Brains were collected 30 minutes, 24 hours, 48 hours, 7 days, and 14 days following the last injection. The paraventricular nucleus of the hypothalamus, central amygdala, and bed nucleus of the stria terminalis were processed for quantitative reverse transcriptase PCR measurement of CRF and CRFR1 mRNA. Additional rats received SNC80 during early cocaine withdrawal, and CRF mRNA was measured in the central amygdala. RESULTS CRF mRNA was elevated in the central amygdala at 24 hours and the paraventricular nucleus at 48 hours of cocaine withdrawal in males and females. Significant sex differences in cocaine-induced CRF upregulation were found in the bed nucleus of the stria terminalis at 30 minutes and 24 hours. SNC80 administration attenuated the increase in CRF mRNA in the central amygdala of female rats only. CONCLUSIONS CRF mRNA regulation during cocaine withdrawal is sex, time, and brain region dependent. Administration of a delta opioid receptor agonist during early withdrawal may ameliorate stress-related negative affect in females by abrogating the induction of CRF mRNA.

中文翻译：

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慢性可卡因后大鼠杏仁扁桃体中CRF mRNA的调节：性别差异和δ阿片受体激动作用。

背景技术可卡因戒断激活了压力系统。女性更容易因使用可卡因而复发，对戒断所引起的负面影响更敏感。三角洲阿片受体调节可卡因戒断大鼠的焦虑样行为。这项研究测量了雄性和雌性大鼠中一种主要应激肽，促肾上腺皮质激素释放因子（CRF）及其1型受体的基因调控的时间过程，以及δ阿片受体激动剂SNC80标准化可卡因的能力。戒断引起的CRF mRNA改变。方法大鼠每天注射3次可卡因或生理盐水，共14天。最后一次注射后30分钟，24小时，48小时，7天和14天收集大脑。下丘脑室旁核，中央杏仁核，处理末端纹状体的床核，用于定量逆转录酶PCR检测CRF和CRFR1 mRNA。在可卡因早期戒断期间，另一些大鼠接受了SNC80，并在杏仁中央部位测量了CRF mRNA。结果在男性和女性中，可卡因撤药后24小时，中央杏仁核中CRF mRNA升高，而在48小时时，脑室旁核中CRF mRNA升高。在30分钟和24小时时，可卡因诱导的CRF上调的显着性别差异在终末皮层的床核中发现。SNC80给药仅减弱雌性大鼠中央杏仁核中CRF mRNA的增加。结论可卡因戒断过程中CRF mRNA的调节取决于性别，时间和大脑区域。