Davidson College, Psychology Department, Davidson, NC 28036, United States; Lake Forest College, Psychology Department, Lake Forest, IL 60045, United States.
Davidson College, Psychology Department, Davidson, NC 28036, United States.
Drug Alcohol Depend. 2024 Nov 1;264:112450. doi: 10.1016/j.drugalcdep.2024.112450. Epub 2024 Sep 16.
The combination of fentanyl and xylazine (i.e., "tranq-dope") was recently declared an emerging national health threat in the United States. Given the recency of this development, very little is known regarding the behavioral pharmacology of fentanyl-xylazine combinations. The purpose of this study was to characterize the somatic and affective withdrawal symptoms of this drug combination.
Male and female Long Evans rats were given twice daily (08:00 and 20:00) subcutaneous injections of fentanyl, xylazine, or combined fentanyl-xylazine for five days. On the sixth (testing) day, rats were given a final injection at 08:00. Four hours later, rats were injected intraperitoneally with either saline or a naloxone challenge before behavioral observation. Somatic withdrawal was examined using the Gellert-Holtzman scale and anxiety-like behavior was examined using the elevated plus maze.
Naloxone administration did not induce somatic or affective symptoms in rats treated with fentanyl alone, a low dose of xylazine alone, or a high dose of xylazine alone. Naloxone induced somatic but not affective withdrawal symptoms in rats treated with both fentanyl and xylazine.
Chronic co-exposure to fentanyl and xylazine produces an opioid-like somatic withdrawal syndrome at doses that are not apparent with either drug alone. These results corroborate clinical reports that xylazine worsens fentanyl withdrawal and suggest that novel interventions may be required to treat withdrawal from fentanyl-xylazine combinations in humans.
芬太尼和二甲噻嗪（即“tranq-dope”）的组合最近在美国被宣布为一种新出现的国家健康威胁。鉴于这一发展的新近性，对于芬太尼-二甲噻嗪组合的行为药理学知之甚少。本研究的目的是描述这种药物组合的躯体和情感戒断症状。
雄性和雌性长耳大仓鼠每天两次（08:00 和 20:00）皮下注射芬太尼、二甲噻嗪或芬太尼-二甲噻嗪混合物，共五天。第六天（测试日），大鼠在 08:00 时接受最后一次注射。四小时后，大鼠接受盐水或纳洛酮挑战的腹腔注射，然后进行行为观察。使用 Gellert-Holtzman 量表检查躯体戒断，使用高架十字迷宫检查焦虑样行为。
纳洛酮给药不会在单独接受芬太尼、单独接受低剂量二甲噻嗪或单独接受高剂量二甲噻嗪的大鼠中引起躯体或情感症状。在同时接受芬太尼和二甲噻嗪治疗的大鼠中，纳洛酮诱导躯体戒断症状，但不诱导情感戒断症状。
慢性共同暴露于芬太尼和二甲噻嗪会产生阿片样的躯体戒断综合征，而单独使用任何一种药物都不会出现这种情况。这些结果与临床报告一致，即二甲噻嗪会加重芬太尼戒断，并表明可能需要新的干预措施来治疗人类芬太尼-二甲噻嗪混合物的戒断。
