TOLERANCE TO SELF-ADMINISTRATION OF COCAINE IN RATS - TIME-COURSE AND DOSE-RESPONSE DETERMINATION USING A MULTIDOSE METHOD
TOLERANCE TO SELF-ADMINISTRATION OF COCAINE IN RATS - TIME-COURSE AND DOSE-RESPONSE DETERMINATION USING A MULTIDOSE METHOD
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DOI：
10.1016/0376-8716(93)90089-9
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发表时间：
1993-05-01
影响因子：
4.2
通讯作者：
LANE, JD
中科院分区：
文献类型：
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作者：
EMMETTOGLESBY, MW;PELTIER, RL;LANE, JD
为了评估在自我给药范例中对可卡因的耐受性，训练大鼠以固定比率2（FR 2）强化时间表自我给药可卡因（0.25 mg/注射）。在可卡因的慢性给药（20 mg/kg/8 h，持续10天）期间研究了耐受性的发展，可卡因的给药可以是偶然的（由大鼠自行给药），也可以是非偶然的（由实验者输注）。可卡因的偶然和非偶然给药都产生了相当的耐受性，可卡因自我给药的速度更快（平均强化时间IS（R）T显着下降）表明了这一点。耐受性在慢性方案的第2天形成，并从第4天至第10天达到下限值（基线的60%）。终止慢性可卡因治疗后，耐受性恢复，IS（R）Ts在终止治疗后6天内恢复至基线水平。第二组实验确定是否可以使用多剂量方法研究耐受性，以在单次给药中获得剂量反应数据。一个多泵系统允许在一个实验阶段测试三个剂量的可卡因。从多剂量方法获得的剂量-反应曲线：（i）与从单剂量方法获得的剂量-反应曲线无差异;（ii）具有重现性;（iii）通过Schering 23390向右移动。然后对大鼠进行为期7天的可卡因（20 mg/kg/8 h）或盐水输注慢性方案。在这个慢性可卡因期结束时，他们用多剂量方法进行了测试。与慢性生理盐水相比，慢性可卡因使可卡因剂量-反应曲线向右移动，表明多剂量方法可以成功地应用于证明对自我给药范例中可卡因作用的耐受性。
To assess tolerance to cocaine in a self-administration paradigm, rats were trained to self-administer cocaine (0.25 mg/injection) on a fixed-ratio 2 (FR2) schedule of reinforcement. The development of tolerance was studied during chronic administration of cocaine (20 mg/kg per 8 h for 10 days), given either contingently (self-administered by the rats) or non-contingently (infused by the experimenter). Both contingent and non-contingent administration of cocaine produced comparable tolerance, as indicated by a faster rate of cocaine self-administration (the average inter-reinforcer time, IS (R)T, decreased significantly). Tolerance developed by day 2 of the chronic regimen and reached a floor value (60% of baseline) from day 4 through day 10. Termination of chronic cocaine then resulted in recovery from tolerance, with IS (R)Ts returning to baseline within 6 days of termination. A second set of experiments determined whether tolerance could be studied using a multi-dose method to obtain dose-response data in a single session. A system of multiple pumps allowed testing of three doses of cocaine during a single experimental session. Cocaine dose-response curves obtained from the multi-dose method: (i) did not differ from that obtained from a single-dose method; (ii) were reproducible; and (iii) were shifted to the right by Schering 23390. Rats were then subjected to a 7-day chronic regimen of infused cocaine (20 mg/kg per 8 h) or infused saline. At the end of this chronic cocaine period, they were tested with the multi-dose method. Chronic cocaine, as compared to chronic saline, shifted the cocaine dose-response curve to the right, indicating that the multi-dose method can be successfully applied to demonstrate tolerance to the effects of cocaine in a self-administration paradigm.