Zarrindast Mohammad-Reza, Sarahroodi Shadi, Arzi Ardeshir, Khodayar Mohammad Javad, Taheri-Shalmani Saba, Rezayof Ameneh
Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.
Behav Pharmacol. 2008 Oct;19(7):716-23. doi: 10.1097/FBP.0b013e3283123c83.
Cannabinoids, which are the active compounds of marijuana, produce some pharmacological effects similar to the opioids. In addition, there are functional interactions between the cannabinoid and opioid systems. In this study, we investigated the effects of intraperitoneal (i.p.) injection of opioid drugs on responses induced by intracentral amygdala (intra-CeA) microinjection of cannabinoid CB1 receptor agents in rats, using the elevated plus maze test of anxiety. I.p. injection of morphine (6 and 9 mg/kg) 30 min before testing, increased the percentage open arm time (%OAT) and the percentage open arm entries (%OAE), but not locomotor activity, showing an anxiolytic-like response. I.p. administration of the opioid receptor antagonist, naloxone (1 mg/kg) 15 min before testing, significantly reduced %OAT, but not %OAE and locomotor activity. The drug, however, tended to decrease locomotor activity. Intra-CeA administration of arachidonylcyclopropylamide (ACPA, an agonist shown to selectively activate CB1 receptors; 1.25 and 5 ng/rat) increased %OAT and %OAE but not locomotor activity, indicating an anxiolytic-like response. Coadministration of morphine (6 mg/kg, i.p.) plus ACPA (0.125 ng/rat, intra-CeA) increased the anxiolytic-like response. Administration of naloxone reversed the effects of intra-CeA injection of ACPA. Intra-CeA administration of the cannabinoid CB1 receptor antagonist, AM251 (2.5, 25, and 100 ng/rat) did not alter %OAT and %OAE, but the higher doses of the drug (25 and 100 ng/rat) reduced locomotor activity. Coadministration of morphine (6 mg/kg) or naloxone (0.1 mg/kg) with AM251 showed an anxiolytic-like response. In conclusion, the results may indicate an anxiolytic-like effect for cannabinoid CB1 receptors of the CeA and the existence of an interaction between the cannabinoid and the opioid systems in the modulation of anxiety.
大麻素是大麻中的活性成分，其产生的一些药理作用与阿片类药物相似。此外，大麻素系统和阿片类系统之间存在功能相互作用。在本研究中，我们使用高架十字迷宫焦虑试验，研究了腹腔注射阿片类药物对大鼠中央杏仁核内注射大麻素CB1受体激动剂所诱导反应的影响。在测试前30分钟腹腔注射吗啡（6毫克/千克和9毫克/千克），增加了开臂时间百分比（%OAT）和开臂进入百分比（%OAE），但不影响运动活性，显示出类似抗焦虑的反应。在测试前15分钟腹腔注射阿片受体拮抗剂纳洛酮（1毫克/千克），显著降低了%OAT，但不影响%OAE和运动活性。然而，该药物倾向于降低运动活性。中央杏仁核内注射花生四烯酰环丙酰胺（ACPA，一种显示可选择性激活CB1受体的激动剂；1.25纳克/只大鼠和5纳克/只大鼠）增加了%OAT和%OAE，但不影响运动活性，表明有类似抗焦虑的反应。吗啡（6毫克/千克，腹腔注射）与ACPA（0.125纳克/只大鼠，中央杏仁核内注射）联合给药增强了类似抗焦虑的反应。纳洛酮给药逆转了中央杏仁核内注射ACPA的作用。中央杏仁核内注射大麻素CB1受体拮抗剂AM251（2.5纳克/只大鼠、25纳克/只大鼠和100纳克/只大鼠）未改变%OAT和%OAE，但较高剂量的该药物（25纳克/只大鼠和100纳克/只大鼠）降低了运动活性。吗啡（6毫克/千克）或纳洛酮（0.1毫克/千克）与AM251联合给药显示出类似抗焦虑的反应。总之，结果可能表明中央杏仁核的大麻素CB1受体具有类似抗焦虑的作用，并且在焦虑调节中大麻素系统和阿片类系统之间存在相互作用。
