Liu Yu, Roberts David C S, Morgan Drake
Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Psychopharmacology (Berl). 2005 May;179(3):644-51. doi: 10.1007/s00213-004-2089-y. Epub 2005 Jan 14.
Animal models that identify the effects of self-administration histories on subsequent patterns, levels of intake, and other aspects of reinforcement will help clarify the controlling variables of human drug use.
Identify the effects of extended-access to cocaine and 1 or 7 days of deprivation on cocaine-maintained breakpoints on a progressive ratio (PR) schedule of reinforcement.
Male, Sprague-Dawley rats were trained to self-administer intravenous cocaine (expt 1: 1.5 mg/kg per infusion; expt 2: 0.75 mg/kg per infusion), and then given various histories of self-administration and deprivation. Breakpoints, the number of infusions self-administered on a PR schedule, were assessed following the deprivation period.
Rates of cocaine intake increased when access to cocaine was extended to 6 h/day. From day 1 to day 14, daily intake increased from 92 (+/-2.5) to 101 (+/-2.8) mg/kg in expt 1, and from 55 (+/-4) to 78 (+/-2.2) mg/kg in expt 2. Total intake across this 2-week period was approximately 1260 and 970 mg/kg in expts 1 and 2. Breakpoints were not different following this escalation period. The introduction of a 7-day deprivation period failed to alter breakpoints.
There is dissociation between changes in rate of cocaine intake (or consumption) and breakpoints maintained on a PR schedule. Extended-access to cocaine produced increases in rate of intake without altering breakpoints. Depending on the experimental question, extended-access conditions may prove useful for studying changes in certain aspects of reinforcement, such as consumption, but not others, such as the strength of a drug as a reinforcer.
能够确定自我给药史对后续模式、摄入量水平及强化作用其他方面影响的动物模型,将有助于阐明人类药物使用的控制变量。
确定延长获取可卡因的时间以及1天或7天的剥夺期对按渐进比率(PR)强化程序维持的可卡因断点的影响。
雄性Sprague-Dawley大鼠接受静脉注射可卡因的自我给药训练(实验1:每次注射1.5毫克/千克;实验2:每次注射0.75毫克/千克),然后给予不同的自我给药和剥夺史。在剥夺期后评估断点,即按PR程序自我给药的注射次数。
当获取可卡因的时间延长至每天6小时时,可卡因摄入量增加。在实验1中,从第1天到第14天,每日摄入量从92(±2.5)毫克/千克增加到101(±2.8)毫克/千克;在实验2中,从55(±4)毫克/千克增加到78(±2.2)毫克/千克。在这两周期间,实验1和实验2的总摄入量分别约为1260毫克/千克和970毫克/千克。在这个递增期后,断点没有差异。引入7天的剥夺期未能改变断点。
可卡因摄入量(或消耗量)的变化与按PR程序维持的断点之间存在分离。延长获取可卡因的时间会使摄入量增加,但不会改变断点。根据实验问题,延长获取条件可能对研究强化作用某些方面的变化(如消耗量)有用,但对其他方面(如药物作为强化物的强度)则不然。