McMillan D E, Leander J D, Wilson T W, Wallace S C, Fix T, Redding S, Turk R T
J Pharmacol Exp Ther. 1976 Feb;196(2):269-79.
Rats drank solutions of narcotic analgesics as the only drinking fluid available in their cages. Relative to their daily water intake before the drug solutions were introduced, the rats drank more etonitazene solution, less methadone solution, and about the same volume of morphine, meperidine and levorphanol solution as water, although some rats would not drink the higher concentrations of morphine (1.0 mg/ml), levorphanol (1.0 mg/ml) and methadone (1.0 mg/ml). When naloxone (1.0 mg/kg) was administered after 12 days of drinking the drug solutions, the severity of the abstinence syndromes based on scoring of symptoms and on weight loss was morphine greater than or equal to etonitazine greater than levorphanol greater than meperidine greater than methadone. The animals showing the most severe syndrome after naloxone usually consumed more drug solution than usual during the next 24 hours, so that body weights were normal at the end of the 24-hour period. Nonprecipitated abstinence was also studied in these rats by replacing the drug solutions with water 3 to 5 days after the naloxone injection. Rats that had been drinking morphine, etonitazene and levorphanol lost weight for 2 or 3 days and then began to regain their lost weight. In contrast, rats which had been switched from methadone and meperidine solutions to water gained weight rapidly. Morphine and etonitazene drinkers which had been switched to water drank a lesser volume of water than they had been drinking of drug solution whereas some ex-methadone drinkers drank more water.
大鼠饮用麻醉性镇痛药溶液作为其笼中唯一可获得的饮用水。相对于引入药物溶液之前的每日饮水量,大鼠饮用更多的依托尼秦溶液,较少的美沙酮溶液,并且饮用吗啡、哌替啶和左啡诺溶液的量与水大致相同,尽管一些大鼠不会饮用较高浓度的吗啡(1.0毫克/毫升)、左啡诺(1.0毫克/毫升)和美沙酮(1.0毫克/毫升)。在饮用药物溶液12天后给予纳洛酮(1.0毫克/千克)时,基于症状评分和体重减轻的戒断综合征严重程度为吗啡≥依托尼秦>左啡诺>哌替啶>美沙酮。在给予纳洛酮后表现出最严重综合征的动物通常在接下来的24小时内比平时消耗更多的药物溶液,以至于在24小时结束时体重恢复正常。在这些大鼠中,还通过在纳洛酮注射后3至5天将药物溶液换成水来研究非突发性戒断。饮用吗啡、依托尼秦和左啡诺的大鼠体重减轻2或3天,然后开始恢复体重。相比之下,从美沙酮和哌替啶溶液换成水的大鼠体重迅速增加。从药物溶液换成水的吗啡和依托尼秦饮用者饮用的水量比饮用药物溶液时少,而一些从前饮用美沙酮的大鼠饮用的水更多。