Sorge Robert E, Stewart Jane
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada.
Psychopharmacology (Berl). 2005 Dec;183(2):210-7. doi: 10.1007/s00213-005-0160-y. Epub 2005 Nov 9.
There is reason to think that footshock stress-induced reinstatement of cocaine may be affected by the history of drug use and time since termination of drug taking.
Here, we assessed the contribution of daily access (hours per day) and duration (number of days) of cocaine self-administration to propensity to reinstate drug seeking following footshock stress at three time points following cocaine self-administration.
Rats were trained to self-administer cocaine (0.5 mg kg(-1) infusion(-1)) on a fixed ratio 1 schedule in one of four training combinations of hours per day and number of days [2/7, 2/21, 12/7, and 12/21 (h/day)]. Rats were then tested for the first time under extinction conditions at either day 1, 10, or 60 after termination of cocaine availability. Once extinction criterion was met (<15 lever presses in 1 h), rats were then tested for stress-induced reinstatement after 15 min of intermittent, inescapable footshock (0.8 mA, 0.5 s/shock, mean off period of 40 s).
Rats that were given 12-h access to cocaine during training responded less in tests of extinction than those rats given 2-h access. Rats in all groups tested in extinction at days 10 and 60 showed higher responding than at day 1, suggesting an incubation of responding. In footshock stress-induced reinstatement tests, rats with greater exposure to cocaine showed a similar suppression of responding at day 1 and enhanced responding at day 60. As expected, rats that were given 12-h/21-day access to cocaine had the greatest intake of cocaine across the training phase with a slow escalation of hourly intake.
Greater access to cocaine results in suppression of cocaine seeking following footshock stress at early time points and a progressive increase over time.
有理由认为，足部电击应激诱导的可卡因复吸可能会受到药物使用史以及停药后时间的影响。
在此，我们评估了可卡因自我给药的每日使用时长（每天小时数）和持续时间（天数）对可卡因自我给药后三个时间点足部电击应激后恢复觅药倾向的影响。
大鼠在每天小时数和天数的四种训练组合[2/7、2/21、12/7和12/21（小时/天）]之一中，按照固定比率1的程序接受训练以自我给药可卡因（0.5毫克/千克注射量）。然后在可卡因供应终止后的第1天、第10天或第60天，首次在消退条件下对大鼠进行测试。一旦达到消退标准（1小时内杠杆按压次数<15次），然后在15分钟间歇性、不可逃避的足部电击（0.8毫安，每次电击0.5秒，平均间隔期40秒）后，对大鼠进行应激诱导的复吸测试。
在训练期间有12小时可接触可卡因的大鼠在消退测试中的反应比有2小时可接触可卡因的大鼠少。在第10天和第60天进行消退测试的所有组中的大鼠显示出比第1天更高的反应，表明反应在潜伏期。在足部电击应激诱导的复吸测试中，接触可卡因更多的大鼠在第1天表现出类似的反应抑制，而在第60天反应增强。正如预期的那样，在训练阶段有12小时/21天可接触可卡因的大鼠可卡因摄入量最大，且每小时摄入量缓慢增加。
更多接触可卡因会导致在早期时间点足部电击应激后可卡因觅药行为受到抑制，且随着时间的推移逐渐增加。
