Department of Psychology, University of Kentucky, Lexington, KY, USA.
Biomedical Biological Science Research Building, University of Kentucky, Room 447, 741 S. Limestone, Lexington, KY, 40536-0509, USA.
Psychopharmacology (Berl). 2021 Aug;238(8):2261-2273. doi: 10.1007/s00213-021-05850-7. Epub 2021 Apr 24.
Escalation of drug intake and craving are two DSM-5 hallmark symptoms of opioid use disorder (OUD).
This study determined if escalation of intake as modeled by long access (LgA) self-administration (SA) and craving measured by reinstatement are related.
Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl across 7 daily 1-h short access (ShA) sessions, followed by 21 SA sessions of either 1- or 6-h duration (ShA or LgA). Following 14 1-h extinction sessions, Experiment 1 assessed reinstatement induced by either fentanyl (10 or 30 µg/kg) or yohimbine (1 or 2 mg/kg), and Experiment 2 assessed reinstatement induced by a drug-associated cue light.
Females acquired fentanyl SA faster than males. When shifted to LgA sessions, LgA rats escalated fentanyl intake, but ShA rats did not; no reliable sex difference in the rate of escalation was observed. In extinction, compared to ShA rats, LgA rats initially responded less and showed less decay of responding across sessions. A priming injection of fentanyl induced reinstatement, with LgA rats reinstating more than ShA rats at the 30 µg/kg dose. Yohimbine (1 mg/kg) also induced reinstatement, but there was no effect of access group or sex. With cue-induced reinstatement, LgA females reinstated less than LgA males and ShA females.
Among the different reinstatement tests assessed, escalation of fentanyl SA increased only drug-primed reinstatement, suggesting a limited relationship between escalation of drug intake and craving (reinstatement) for OUD.
药物摄入增加和渴望是 DSM-5 阿片类药物使用障碍（OUD）的两个标志症状。
本研究旨在确定通过长时程（LgA）自我给药（SA）建模的摄入增加与渴望（通过复吸来测量）之间的关系。
成年雄性和雌性 Sprague-Dawley 大鼠接受芬太尼的自我给药训练，每天进行 7 次 1 小时短时间访问（ShA），随后进行 21 次 1 小时或 6 小时时长的 SA（ShA 或 LgA）。在进行了 14 次 1 小时的消退训练后，实验 1 评估了芬太尼（10 或 30μg/kg）或育亨宾（1 或 2mg/kg）诱导的复吸，实验 2 评估了药物相关线索光诱导的复吸。
雌性大鼠比雄性大鼠更快地获得芬太尼 SA。当切换到 LgA 时，LgA 大鼠增加了芬太尼的摄入量，但 ShA 大鼠没有；在增加速度上没有可靠的性别差异。在消退阶段，与 ShA 大鼠相比，LgA 大鼠最初的反应较少，并且在整个实验过程中反应的衰减较小。芬太尼的预注射诱导了复吸，LgA 大鼠在 30μg/kg 剂量下的复吸比 ShA 大鼠更多。育亨宾（1mg/kg）也诱导了复吸，但访问组或性别没有影响。在线索诱导的复吸中，LgA 雌性大鼠的复吸量少于 LgA 雄性大鼠和 ShA 雌性大鼠。
在所评估的不同复吸测试中，芬太尼 SA 的增加仅增加了药物诱导的复吸，这表明 OUD 患者药物摄入增加和渴望（复吸）之间的关系有限。
