Norman A B, Norman M K, Hall J F, Tsibulsky V L
Division of Neuroscience, Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0559, USA.
Brain Res. 1999 Jun 12;831(1-2):165-74. doi: 10.1016/s0006-8993(99)01423-7.
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 microg 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 microg 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.
据报道，静脉注射可卡因能可靠地恢复（引发）动物对可卡因的自我给药行为。我们在此报告，在经过训练可自我给药可卡因的大鼠中存在一个可卡因引发阈值。可卡因引发阈值被定义为体内能恢复已维持的可卡因自我给药行为的可卡因最低水平。经计算，大鼠的平均可卡因引发阈值约为186至212微克/千克（-1）。因此，任何导致体内可卡因水平等同于单次静脉注射该剂量范围所产生水平的注射、一系列注射或持续输注，都会恢复可卡因的自我给药行为。D（1）多巴胺受体拮抗剂SCH23390（10微克/千克（-1），静脉注射）可显著提高引发阈值，表明多巴胺能神经传递发挥了作用。从7天的右旋苯丙胺输注中撤药后，引发阈值升高，但维持自我给药的注射间隔时间未变。此外，可卡因引发阈值与维持可卡因自我给药的注射间隔时间之间没有相关性。因此，恢复可卡因自我给药行为的潜在机制与维持可卡因自我给药行为的潜在机制不同，且它们受到不同的调节。引发阈值有可能代表了药物研发的一个独特靶点。
