Different methods establish a rat model of morphine drug discrimination with a fixed ratio 10
10.16438/j.0513-4870.2021-0132
- VernacularTitle:不同方法建立固定比率为10的大鼠吗啡药物辨别模型
- Author:
Huan ZHANG
1
,
2
;
Shu-zhe WANG
1
,
2
;
Bei-bei LI
3
;
Yi-ming WANG
4
;
Xiao-zhen LIU
3
,
5
;
Hua-ying CHEN
3
;
Yun-liang QIU
3
Author Information
1. College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
2. Shanghai InnoStar Bio-Tech Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai 201203, China
3. Shanghai InnoStar Bio-Tech Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai 201203, China
4. School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
5. School of Pharmacy, Fudan University, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
morphine;
rug discrimination;
ependence;
safety evaluation;
rug abuse
- From:
Acta Pharmaceutica Sinica
2021;56(7):1921-1926
- CountryChina
- Language:Chinese
-
Abstract:
In this study, a rat morphine drug discrimination model with a fixed ratio (FR) of 10 (FR10) was established using different methods to explore which methods can shorten the modeling time and test the dose-response relationship and median effective dose (ED50) value. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of Shanghai InnoStar Bio-tech Co., Ltd. Forty rats were initially shaped to press lever under a fixed-ratio schedule of food reinforcement. The animals that were successfully trained under a FR10 schedule of food reinforcement were divided into two groups, namely the single-lever + double-lever training group 1 and the double-lever training group 2. In each group, rats were trained to discriminate morphine at 5.6 mg·kg-1 from saline by the intraperitoneal route. After training, different doses of morphine were used to substitute for training dose of morphine, the dose-response curve for morphine were identified in rats, and the ED50 value was calculated. The results showed that, in food training phase: 34 rats successfully entered the discrimination training during food training; in discrimination training phase: 14 animals in group 1 met the discrimination training standard for the first time, which took about (40.71 ± 2.93) days, and there were 13 animals in group 2 that met the discrimination training criteria for the first time, and it took about (51.15 ± 2.55) days. It can be seen that the method of single-lever + double-lever training is better than single-lever training, and the difference is significant compared with group 1 (P ˂ 0.05); in generalization test phase: there are 17 rats completed morphine generalization test, and the percentages of morphine-lever responses produced by the generalization test of different doses of morphine (0, 0.1, 0.5, 1, 3, 5.6, and 10 mg·kg-1) were (9.56 ± 3.13) %, (9.01 ± 5.83) %, (13.82 ± 7.95) %, (29.04 ± 10.13) %, (41.70 ± 10.65) %, (85.36 ± 7.16) %, (94.56 ± 2.76) %, respectively. The results showed that the discriminative stimulative effect induced by morphine dose between 0-10 mg·kg-1 increased in a dose-dependent manner, producing a good dose-response curve, and the ED50 value of morphine was 4.74 mg·kg-1 by linear fitting. The above results showed that, the FR10 morphine drug discrimination model has been successfully established using different methods; the single-lever + double-lever training method is better than the single-lever training, and can relatively shorten the discrimination training cycle.
