Lê A D, Quan B, Juzytch W, Fletcher P J, Joharchi N, Shaham Y
Biobehavioral Research Department, Addiction Research Foundation of Ontario, Toronto, Canada.
Psychopharmacology (Berl). 1998 Jan;135(2):169-74. doi: 10.1007/s002130050498.
Previous studies using a reinstatement procedure have found that acute reexposure to the self-administered drug and exposure to footshock stress reinstate heroin and cocaine seeking after prolonged drug-free periods. Here we tested whether these findings generalize to alcohol-taking behavior. Male rats were initially allowed to consume alcohol in a two-bottle choice procedure (water versus alcohol) for 30 min/day for 36 days. Rats were then trained for 60 min/day in operant chambers to press a lever for the drug (0.13 ml of 12% w/v of an alcohol solution) for up to 55 days. After stable drug-taking on a fixed-ratio-3 schedule of reinforcement was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 4-9 days. Reinstatement of drug seeking was then determined after non-contingent priming injections of alcohol (0.24 and 0.48 g/kg; given i.p. and orally) or exposure to intermittent footshock stress (5 and 15 min; 0.8 mA). Priming injections of alcohol produced a modest dose-dependent reinstatement of drug seeking, whereas footshock stress potently reinstated extinguished alcohol seeking. In contrast, similar parameters of footshock failed to reinstate extinguished sucrose-taking behavior in rats previously trained to lever press for sucrose pellets. These findings extend previous reports on reinstatement of cocaine and heroin seeking by a footshock stressor and by priming drug injections. It also appears that the reinstatement procedure provides an appropriate methodology to study relapse to alcohol-taking behavior in the drug-free state.
以往使用恢复程序的研究发现，在长时间戒断后，急性再次接触自行给药的药物以及暴露于足部电击应激会恢复对海洛因和可卡因的觅药行为。在此，我们测试了这些发现是否适用于饮酒行为。雄性大鼠最初在双瓶选择程序（水与酒精）中每天饮用酒精30分钟，持续36天。然后，大鼠每天在操作箱中训练60分钟，按压杠杆以获取药物（0.13毫升12%重量/体积的酒精溶液），持续长达55天。在获得固定比例为3的强化给药方案下稳定的药物摄取后，通过终止药物递送4 - 9天来消除按压杠杆获取酒精的行为。然后在非条件性注射酒精（0.24和0.48克/千克；腹腔注射和口服）或暴露于间歇性足部电击应激（5和15分钟；0.8毫安）后，确定觅药行为的恢复情况。注射酒精引发了适度的剂量依赖性觅药行为恢复，而足部电击应激有力地恢复了已消除的酒精觅药行为。相比之下，类似参数的足部电击未能恢复先前训练按压杠杆获取蔗糖颗粒的大鼠已消除的蔗糖摄取行为。这些发现扩展了先前关于足部电击应激源和注射引发药物恢复可卡因和海洛因觅药行为的报道。恢复程序似乎也为研究无药状态下饮酒行为的复发提供了一种合适的方法。
