Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system
Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system
复制标题
DOI：
10.1016/s0014-2999(01)00766-x
复制
发表时间：
2001-02-16
影响因子：
5
通讯作者：
Sala, M
中科院分区：
文献类型：
--
作者：
Braida, D;Pozzi, M;Sala, M
以大鼠为实验对象，研究了CP 55,940{(-)-顺式-3-[2-羟基-4-（1,1-二甲基庚基）苯基]-反式-4-（3-羟丙基）环hesanol}、海洛因和乙硝基对脑室内（i.c.v）自我给药的影响。在连续强化计划下，动物每天训练1小时，按两个主动杠杆获得每种药物的载体。然后，当达到一个稳定的基线时，每种药物都可以通过按在训练中发现的不太受欢迎的杠杆来自我施用，而车辆则来自另一个。注射单位剂量增加的CP 55,940（0.1、0.2、0.4、0.8、1.6杯/2 μ l/次）、海洛因（0.125、0.25、0.5、1,2杯/2 μ l/次）或依替唑烯（0.1-0.2-0.5-1杯/2 μ l/次）和相应载体的注射时，条压次数采用对称抛物线拟合。平均药物摄入量与自我给药对数呈线性相关。SR141716A [n -哌啶-5-（4-氯苯基）1-（2,4-二氯苯基）-4-甲基吡唑-3-羧酰胺]（0.5 mg/kg）或纳洛酮HCl （2 mg/kg/i.p）预处理。每天治疗前15分钟减少了cp55,940和海洛因的自我给药。与单独使用每种药物的最大强化单位剂量相比，cp55,940与海洛因或依托硝嗪联合使用可减少药物相关杠杆按压次数。这些发现表明阿片类药物和大麻素系统之间可能存在强烈的相互作用。(C) 2001 Elsevier Science B.V.版权所有
The effect of CP 55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclo-hesanol}, heroin and etonitazene on intracerebroventricular (i.c.v.) self-administration in a free-choice procedure was evaluated in rats. Animals were trained in 1-h daily sessions with a continuous reinforcement schedule to press two active levers to obtain the vehicle of each drug. Then, when a stable baseline was reached, each drug could be self-administered by pressing the lever found to be less preferred during training, while the vehicle came from the other. The number of bar pressings associated with the delivery of increasing unit doses of CP 55,940 (0.1, 0.2, 0.4, 0.8, 1.6 mug/2 mul/infusion), heroin (0.125, 0.25, 0.5, 1, 2 mug/2 mul/infusion) or etonitazene (0.1-0.2-0.5-1 mug/2 mul/infusion) and with the delivery of the corresponding vehicle was fitted by symmetrical parabolas. The mean drug intake was linearly related to the log of self-administered drugs. Pretreatment with SR141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro-phenyl)-4-methylpyrazole-3-carboxamide] (0.5 mg/kg) or naloxone HCl (2 mg/kg/i.p.) 15 min before each daily session reduced the self-administration of both CP 55,940 and heroin. The combination of CP 55,940 with heroin or etonitazene reduced the number of drug-associated lever pressings compared to that obtained with the maximal reinforcing unit dose of each drug alone. These findings suggest there may be a strong interaction between opioids and the cannabinoid system. (C) 2001 Elsevier Science B.V. All rights reserved.