Lobarinas E, Lau C E, Falk J L
Department of Psychology, Rutgers, The State University of New Jersey, Piscataway 08854-8020, USA.
Behav Pharmacol. 1999 Feb;10(1):15-26. doi: 10.1097/00008877-199902000-00002.
This study evaluated whether operant behavior was subject to sensitization upon repeated exposure to cocaine. The behavior of eight rats was reinforced by food-pellet delivery under a differential reinforcement of low-rate (DRL) 45-s schedule, in daily sessions of 190 min. Each session was composed of five 35-min subsessions, with each subsession preceded by a 3-min time out period (TO). For selected sessions, a cumulative dose-effect relation for cocaine, using increasing doses, was first determined by oral gavage administration of a dose during each subsession. Three such cycles were given, separated by between seven and ten sessions. Later, four further cycles were given, using a repetitive 10 mg/kg cocaine per os (p.o.) dose, rather than an increasing dose. Under both dosing procedures, within a cocaine cycle (session), shorter (<45 s) inter-response times (IRT) progressively increased with doses, and reinforced responses decreased. As cycles were repeated, the shorter IRT increases became progressively more marked, indicating the development of sensitization to the effect of cocaine. With the second procedure (repetitive 10 mg/kg doses), reinforcement rate decreases became more marked as cycles were repeated, but this change did not occur using the increasing-dose procedure. Upon later exposure to repetitive 5 mg/kg dosing cycles, none of these rate changes occurred, and performances were equivalent to those occurring under saline cycles. Exposure to cumulative dose regimens of oral cocaine can result in the sensitization of operant behavior to the effects of cocaine.
本研究评估了操作性行为在反复接触可卡因后是否会产生敏化作用。八只大鼠的行为在低比率（DRL）45秒强化程序下通过给予食物颗粒得到强化，每天训练190分钟。每次训练由五个35分钟的子训练组成，每个子训练之前有一个3分钟的暂停期（TO）。对于选定的训练，首先通过在每个子训练期间经口灌胃给予递增剂量的可卡因来确定可卡因的累积剂量效应关系。给予三个这样的周期，中间间隔七到十个训练。之后，给予另外四个周期，使用重复的10毫克/千克可卡因经口（p.o.）剂量，而不是递增剂量。在两种给药程序下，在一个可卡因周期（训练）内，较短（<45秒）的反应间隔时间（IRT）随着剂量的增加而逐渐增加，强化反应减少。随着周期的重复，较短IRT的增加变得越来越明显，表明对可卡因效应产生了敏化作用。在第二种程序（重复10毫克/千克剂量）下，随着周期的重复，强化率的降低变得更加明显，但在递增剂量程序下没有出现这种变化。在后来接触重复的5毫克/千克给药周期时，这些速率变化均未发生，表现与在生理盐水周期下的表现相当。经口给予可卡因的累积剂量方案可导致操作性行为对可卡因效应产生敏化作用。
