Cunningham C L, Henderson C M, Bormann N M
Department of Behavioral Neuroscience and Portland Alcohol Research Center, The Oregon Health Sciences University, 97201-3098, USA.
Psychopharmacology (Berl). 1998 Sep;139(1-2):62-70. doi: 10.1007/s002130050690.
Four experiments examined the effect of naloxone pretreatment on the expression and extinction of ethanol-induced conditioned place preference (experiments 1, 2, 4) or conditioned place aversion (experiments 1, 3). DBA/2 J mice received four pairings of a distinctive tactile (floor) stimulus (CS) with injection of ethanol (2 g/kg) given either immediately before or after 5-min exposure to the CS. A different stimulus was paired with injection of saline. Pre-CS injection of ethanol produced conditioned place preference, whereas post-CS injection of ethanol produced conditioned place aversion. Both behaviors extinguished partially during repeated choice testing after vehicle injection. Naloxone (10 mg/kg) had little effect on the initial expression of conditioned place preference, but facilitated its extinction. Moreover, repeated naloxone testing resulted in the expression of a weak conditioned place aversion to the CS that initially elicited a place preference. In contrast, naloxone (1.5 or 10 mg/kg) enhanced expression of conditioned place aversion, thereby increasing its resistance to extinction. A control experiment (experiment 4) indicated that repeated testing with a different aversive drug, lithium chloride, did not affect rate of extinction or produce an aversion to the CS previously paired with ethanol. These findings do not support the suggestion that naloxone facilitates the general processes that underlie extinction of associative learning. Also, these data are not readily explained by the conditioning of place aversion at the time of testing. Rather, naloxone's effects appear to reflect a selective influence on maintenance of ethanol's conditioned rewarding effect, an effect that may be mediated by release of endogenous opioids. Overall, these findings encourage further consideration of the use of opiate antagonists in the treatment of alcoholism.
四项实验研究了纳洛酮预处理对乙醇诱导的条件性位置偏爱（实验1、2、4）或条件性位置厌恶（实验1、3）的表达及消退的影响。DBA/2 J小鼠接受了四次独特的触觉（地面）刺激（条件刺激）与乙醇注射（2克/千克）的配对，乙醇注射在接触条件刺激前或5分钟接触条件刺激后立即进行。另一种不同的刺激与生理盐水注射配对。在条件刺激前注射乙醇产生了条件性位置偏爱，而在条件刺激后注射乙醇产生了条件性位置厌恶。在注射赋形剂后的重复选择测试中，这两种行为都有部分消退。纳洛酮（10毫克/千克）对条件性位置偏爱的初始表达影响不大，但促进了其消退。此外，重复进行纳洛酮测试导致对最初引发位置偏爱的条件刺激表现出微弱的条件性位置厌恶。相比之下，纳洛酮（1.5或10毫克/千克）增强了条件性位置厌恶的表达，从而增加了其对消退的抵抗力。一项对照实验（实验4）表明，用另一种厌恶药物氯化锂进行重复测试不会影响消退速度，也不会对先前与乙醇配对的条件刺激产生厌恶。这些发现不支持纳洛酮促进联想学习消退背后的一般过程这一观点。此外，这些数据也不能轻易地用测试时位置厌恶的条件作用来解释。相反，纳洛酮的作用似乎反映了对乙醇条件性奖赏效应维持的选择性影响，这种效应可能由内源性阿片类物质的释放介导。总体而言，这些发现鼓励进一步考虑使用阿片类拮抗剂治疗酒精中毒。
