Wiley J L, Barrett R L, Lowe J, Balster R L, Martin B R
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613, USA.
Neuropharmacology. 1995 Jun;34(6):669-76. doi: 10.1016/0028-3908(95)00027-4.
CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in a number of studies as a radioligand for the cannabinoid receptor. This compound shares behavioral and biochemical properties with naturally occurring cannabinoids such as delta 9-THC. The purpose of the present study was 3-fold: to establish the ability of CP 55,940 to serve as a discriminative stimulus, to determine whether this discriminative stimulus is identical to that of delta 9-THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A, would antagonize the discriminative stimulus effects of CP 55,940. Rats were trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever operant conditioning chambers. CP 55,940 produced dose-dependent generalization from the training dose in dose-effect determinations conducted before and after testing with other drugs. The effects of the training dose of CP 55,940 were dose-dependently antagonized by co-administration of SR141716A. Results of substitution tests showed that delta 9-THC, WIN 55,212-2, and cannabinol substituted completely for CP 55,940 in a dose-dependent manner; however, CP 55,940 was approx 10-fold more potent than any of the other drugs in producing CP 55,940-like discriminative stimulus effects. Several drugs with CNS depressant properties (phencyclidine, haloperidol and diazepam) failed to produce reliable substitution for CP 55,940. These results demonstrate that CP 55,940 has discriminative stimulus effects and that it shares these effects with structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
CP 55,940是一种强效合成双环大麻素类似物，已在多项研究中用作大麻素受体的放射性配体。该化合物与天然存在的大麻素如δ9-四氢大麻酚具有行为和生化特性。本研究的目的有三个：确定CP 55,940作为辨别刺激物的能力，确定这种辨别刺激物是否与δ9-四氢大麻酚的相同，以及研究一种新开发的大麻素拮抗剂SR141716A是否会拮抗CP 55,940的辨别刺激作用。在标准的双杠杆操作性条件反射箱中，训练大鼠区分0.1mg/kg的CP 55,940和溶剂。在用其他药物测试之前和之后进行的剂量效应测定中，CP 55,940产生了与训练剂量相关的剂量依赖性泛化。联合给予SR141716A可剂量依赖性地拮抗CP 55,940训练剂量的作用。替代试验结果表明，δ9-四氢大麻酚、WIN 55,212-2和大麻酚以剂量依赖性方式完全替代了CP 55,940；然而，CP 55,940在产生CP 55,940样辨别刺激作用方面比任何其他药物强约10倍。几种具有中枢神经系统抑制特性的药物（苯环利定、氟哌啶醇和地西泮）未能可靠地替代CP 55,940。这些结果表明，CP 55,940具有辨别刺激作用，并且它与结构不同但与CP 55,940一样与大麻素受体结合的化合物共享这些作用。此外，这些作用被大麻素受体拮抗剂SR141716A阻断。（摘要截断于250字）
