De Vries Taco J, Homberg Judith R, Binnekade Rob, Raasø Halfdan, Schoffelmeer Anton N M
Research Institute Neurosciences Vrije Universiteit, Drug Abuse Program, Department of Medical Pharmacology, VU Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
Psychopharmacology (Berl). 2003 Jul;168(1-2):164-169. doi: 10.1007/s00213-003-1422-1. Epub 2003 Apr 1.
Recently, we provided evidence for a cannabinoid mechanism in relapse to cocaine seeking in rats. There is also increasing evidence for functional cross-talk between cannabinoid and opioid systems in several physiological processes.
This study was designed to evaluate whether the cannabinoid system plays a role in mediating the reinforcing and motivational effects of heroin and heroin-paired stimuli.
Male Wistar rats were trained to self-administer heroin (50 microg/kg per infusion) on fixed (FR5) or progressive ratio schedules of reinforcement in the presence of a discriminative and discrete heroin-associated cue. The selective cannabinoid CB1 antagonist SR141716A was given 30 min before the session to determine its effect on responding for heroin. Separate groups of rats were subjected to extinction training during which heroin-associated cues were absent and no heroin was delivered. During subsequent reinstatement tests, the effects of the cannabinoid agonist HU210 and the antagonist SR141716A on reinstatement of heroin seeking were evaluated.
The cannabinoid antagonist dose-dependently reduced responding for heroin on the FR5 schedule and to a greater extent on the progressive ratio schedule. HU210 (20 microg/kg) reinstated heroin seeking behaviour following a 2-week extinction period, whereas SR141716A dose-dependently attenuated heroin seeking that was provoked by a priming injection of heroin (0.25 mg/kg) and heroin seeking that was triggered by re-exposure to heroin paired stimuli.
The results show that the reinforcing and motivational effects of heroin and heroin-paired stimuli are mediated, at least in part, by activation of cannabinoid CB1 receptors. Therefore, the present study provides a rationale for the use of cannabinoid antagonists in the treatment of opiate addiction.
最近，我们提供了大鼠可卡因觅药复发中存在大麻素机制的证据。在多个生理过程中，大麻素系统与阿片系统之间功能性相互作用的证据也日益增多。
本研究旨在评估大麻素系统是否在介导海洛因及海洛因配对刺激的强化和动机效应中发挥作用。
雄性Wistar大鼠在存在辨别性且离散的海洛因相关线索的情况下，接受固定（FR5）或累进比率强化程序训练，以自我给药海洛因（每次输注50微克/千克）。在实验前30分钟给予选择性大麻素CB1拮抗剂SR141716A，以确定其对海洛因反应的影响。将单独的大鼠组进行消退训练，在此期间不存在海洛因相关线索且不给予海洛因。在随后的复吸测试中，评估大麻素激动剂HU210和拮抗剂SR141716A对海洛因觅药复吸的影响。
大麻素拮抗剂在FR5程序上剂量依赖性地减少对海洛因的反应，在累进比率程序上减少的程度更大。HU210（20微克/千克）在2周的消退期后恢复了海洛因觅药行为，而SR141716A剂量依赖性地减弱了由海洛因引发注射（0.25毫克/千克）诱发的海洛因觅药行为以及重新暴露于海洛因配对刺激引发的海洛因觅药行为。
结果表明，海洛因及海洛因配对刺激的强化和动机效应至少部分是由大麻素CB1受体的激活介导的。因此，本研究为使用大麻素拮抗剂治疗阿片类成瘾提供了理论依据。
