Heyne A
Freie Universität Berlin, Institut für Neuropsychopharmakologie, Germany.
Pharmacol Biochem Behav. 1996 Jan;53(1):11-25. doi: 10.1016/0091-3057(95)00193-x.
Opiate intake was studied in rats, which were given free choice between water and etonitazene (ETZ) solutions (2, 4, and 8 mg/l) for 30 weeks. After an abstinence of 19 weeks, the opiate was reoffered. The long-term course of intake could be subdivided in three phases: a period of controlled intake (25 weeks), a period of increasing consumption (week 25-30), and the stage of drug addiction (retest). During controlled intake, environmental and individual variables reversibly influenced ETZ intake (high intake in socially deprived and in subordinate rats, low intake in group-housed and in dominant rats). After 25 weeks of situation-specific intake, the rats spontaneously increased ETZ consumption. In the retest after long-term ETZ-abstinence, their intake was strongly increased compared to both their own intake before and to that of drug-naive controls. ETZ intake could no longer be influenced by environmental, gustatory, or individual factors ("loss of control") indicating opiate addiction. In contrast, rats that have formerly had forced administration by means of a 2 mg/l ETZ solution did not become addicted. Signs of opiate withdrawal, however, occurred in both series of forced and voluntary intake. Principles of the temporal development of opiate addiction are compared with those described previously for ethanol addiction.
对大鼠的阿片类药物摄入量进行了研究，让它们在水和依托尼嗪（ETZ）溶液（2、4和8毫克/升）之间自由选择，持续30周。在禁欲19周后，再次提供阿片类药物。摄入量的长期过程可分为三个阶段：控制摄入期（25周）、摄入量增加期（第25 - 30周）和药物成瘾阶段（重新测试）。在控制摄入期间，环境和个体变量可逆地影响ETZ摄入量（在社会剥夺和从属大鼠中摄入量高，在群居和占主导地位的大鼠中摄入量低）。在特定情境下摄入25周后，大鼠自发增加了ETZ的消耗量。在长期ETZ禁欲后的重新测试中，与它们自己之前的摄入量以及未接触过药物的对照组相比，它们的摄入量大幅增加。ETZ摄入量不再受环境、味觉或个体因素的影响（“失控”），表明出现了阿片类药物成瘾。相比之下，以前通过2毫克/升ETZ溶液强制给药的大鼠没有成瘾。然而，在强制摄入和自愿摄入的两组大鼠中都出现了阿片类药物戒断的迹象。将阿片类药物成瘾的时间发展原则与先前描述的乙醇成瘾原则进行了比较。
