Priming threshold: a novel quantitative measure of the reinstatement of cocaine self-administration
Priming threshold: a novel quantitative measure of the reinstatement of cocaine self-administration
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DOI：
10.1016/s0006-8993(99)01423-7
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发表时间：
1999-06-12
期刊：
影响因子：
2.9
通讯作者：
Tsibulsky, VL
中科院分区：
文献类型：
--
作者：
Norman, AB;Norman, MK;Tsibulsky, VL
据报道，静脉注射可卡因可以可靠地恢复（启动）动物体内可卡因的自我给药。我们在此报告，经过训练自我施用可卡因的大鼠存在可卡因启动阈值。可卡因启动阈值定义为体内可卡因恢复维持的可卡因自我给药的最低水平。经计算，大鼠的平均可卡因启动阈值约为 186 至 212 mu g kg(-1)。因此，任何注射、系列注射或连续输注所产生的可卡因水平相当于该剂量范围的单次静脉注射所产生的水平，都将恢复可卡因自我给药。 D-1多巴胺受体拮抗剂SCH23390（10μg·kg(-1)，静脉注射）显着增加启动阈值，表明多巴胺能神经传递的作用。从 7 天的 D-安非他明输注中撤出后，启动阈值增加，但维持自我给药的注射间隔没有增加。此外，可卡因启动阈值与维持可卡因自我给药的注射间隔之间不存在相关性。因此，恢复可卡因自我给药的机制不同于维持可卡因自我给药的机制，并且它们受到不同的调节。启动阈值可能代表药物开发的不同目标。 (C) 1999 Elsevier Science B.V. 保留所有权利。
The intravenous injection of cocaine has been reported to reliably reinstate (prime) the self-administration of cocaine in animals. We report herein that there is a cocaine priming threshold in rats trained to self-administer cocaine. The cocaine priming threshold is defined as the minimum level of cocaine in the body that will reinstate maintained cocaine self-administration. The mean cocaine priming threshold in rats was calculated to be approximately 186 to 212 mu g kg(-1). Therefore, any injection, series of injections or continuous infusion that result in a level of cocaine equivalent to that produced by a single intravenous injection of this range of doses, will reinstate cocaine self-administration. The priming threshold was significantly increased by the D-1 dopamine receptor antagonist SCH23390 (10 mu g kg(-1), i.v.), indicating a role for dopaminergic neurotransmission. The priming threshold, but not the inter-injection interval of maintained self-administration, was increased following withdrawal from a 7-day infusion of D-amphetamine. In addition, there was no correlation between the cocaine priming threshold and the inter-injection intervals of maintained cocaine self-administration. Therefore, the mechanisms underlying the reinstatement of cocaine self-administration are distinct from the mechanisms underlying the maintenance of cocaine self-administration and they are differentially regulated. It is possible that the priming threshold may represent a distinct target for medications development. (C) 1999 Elsevier Science B.V. All rights reserved.