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剂量和给药时长对大鼠可卡因自我给药的影响。

Effects of dose and session duration on cocaine self-administration in rats.

作者信息

Wee Sunmee, Specio Sheila E, Koob George F

机构信息

Committee on The Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

J Pharmacol Exp Ther. 2007 Mar;320(3):1134-43. doi: 10.1124/jpet.106.113340. Epub 2007 Jan 3.

Abstract

Previous studies showed that an extended 6-h session duration produced an increasing rate of cocaine self-administration in rats. The present study further investigated the effect of dose and session duration on cocaine self-administration. Eight groups of rats (4 doses x 2 session durations) self-administered one of four cocaine doses (0.25, 0.5, 1, and 2 mg/kg/injection) in either 1- or 6-h sessions under a fixed-ratio schedule. In another experiment, two other groups of rats self-administered 0.5 mg/kg/injection of cocaine in either 3- or 12-h sessions. Cocaine self-administration increased at all doses in 6-h sessions but not in 1-h sessions. Cocaine intake (milligram/kilogram) reached an asymptote earlier at a higher dose, but the rate of responding increased faster when the dose was lower. In ShA rats, the cocaine dose-response function was higher in rats at the two higher unit doses than at the lower doses. Cocaine self-administration increased in 6- and 12-h sessions, but not in 1- and 3-h sessions. The increase in self-administration was faster and greater in 12-h sessions than 6-h sessions. The data suggest that cocaine self-administration increases at various doses with prolonged access and that an increase in the rate of responding is positively and inversely associated with session duration and unit dose, respectively. Results also imply that cocaine intake reaches a ceiling faster at high doses even under short session duration. Therefore, high doses or prolonged access to cocaine are more likely to result in a pattern of cocaine intake that reflects compulsive use.

摘要

先前的研究表明,延长至6小时的实验时长会使大鼠可卡因自我给药率增加。本研究进一步探究了剂量和实验时长对可卡因自我给药的影响。八组大鼠(4种剂量×2种实验时长)在固定比率模式下,于1小时或6小时的实验时段内自我给药四种可卡因剂量(0.25、0.5、1和2毫克/千克/注射)中的一种。在另一项实验中,另外两组大鼠在3小时或12小时的实验时段内自我给药0.5毫克/千克/注射的可卡因。在6小时的实验时段内,所有剂量的可卡因自我给药均增加,但在1小时的实验时段内未增加。可卡因摄入量(毫克/千克)在较高剂量时更早达到渐近线,但当剂量较低时反应率增加得更快。在ShA大鼠中,两个较高单位剂量组的大鼠可卡因剂量反应函数高于较低剂量组。可卡因自我给药在6小时和12小时的实验时段内增加,但在1小时和3小时的实验时段内未增加。自我给药的增加在12小时的实验时段内比6小时的实验时段内更快且更大。数据表明,随着获取时间延长,不同剂量的可卡因自我给药均增加,且反应率的增加分别与实验时长和单位剂量呈正相关和负相关。结果还表明,即使在短实验时长下,高剂量可卡因的摄入量也会更快达到上限。因此,高剂量或长时间获取可卡因更有可能导致反映强迫性使用的可卡因摄入模式。

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