Browse > Article
http://dx.doi.org/10.4062/biomolther.2014.064

Dependence Potential of Tramadol: Behavioral Pharmacology in Rodents  

Cha, Hye Jin (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Song, Min Ji (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Lee, Kwang-Wook (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Kim, Eun Jung (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Kim, Young-Hoon (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Lee, Yunje (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Seong, Won-Keun (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Hong, Sa-Ik (School of Pharmacy, Sungkyunkwan University)
Jang, Choon-Gon (School of Pharmacy, Sungkyunkwan University)
Yoo, Han Sang (Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University)
Jeong, Ho-Sang (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
Publication Information
Biomolecules & Therapeutics / v.22, no.6, 2014 , pp. 558-562 More about this Journal
Abstract
Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.
Keywords
Tramadol; Dopamine system; Serotonin system; Drug dependence; Animal behavioral tests;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Sarkar, S., Nebhinani, N., Singh, S. M., Mattoo, S. K. and Basu, D. (2012) Tramadol dependence: a case series from India. Indian J. Psychol. Med. 34, 283-285.   DOI
2 Randall, C. and Crane, J. (2014) Tramadol deaths in northern Ireland: a review of cases from 1996 to 2012. J. Forensic Leg. Med. 23, 32-36.   DOI
3 Ritzmann, R. F. (1981) Opiate dependence following acute injections of morphine and naloxone: the assessment of various withdrawal signs. Pharmacol. Biochem. Behav. 14, 575-577.   DOI   ScienceOn
4 Saelens, J. K., Granat, F. R. and Sawyer, W. K. (1971) The mouse jumping test-a simple screening method to estimate the physical dependence capacity of analgesics. Arch. Int. Pharmacodyn. Ther. 190, 213-218.
5 Smits, S. E. (1975) Quantitation of physical dependence in mice by naloxone-precipitated jumping after a single dose of morphine. Res. Commun. Chem. Pathol. Pharmacol. 10, 651-661.
6 Taylor, C. Z. (2002) Religious addiction: obsession with spirituality. Pastor. Psychology 50, 291-315.   DOI
7 Varlinskaya, E. I. and Spear, L. P. (2002) Acute effects of ethanol on social behavior of adolescent and adult rats: role of familiarity of the test situation. Alcohol Clin. Exp. Res. 26, 1502-1511.   DOI   ScienceOn
8 Way, E. L., Loh, H. H. and Shen, F. H. (1969) Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. Exp. Ther. 167, 1-8.
9 Weeks, J. R. (1972) Long term intraveneous infusion (R. D. Myers, Ed.), pp.155-168. Academic press, New York.
10 Zhang, M., Jing, L., Liu, Q., Wen, R. T., Li, J. X., Li, Y. L., Gong, Q. and Liang, J. H. (2012) Tramadol induces conditioned place preference in rats: interactions with morphine and buprenorphine. Neuroscience Lett. 520, 87-91.   DOI
11 Acheson, S. K., Richardson, R. and Swarzwelder, H. S. (1999) Developmental changes in seizure susceptibility during ethanol withdrawal. Alcohol 18, 23-26.   DOI
12 Bozarth, M. A. (1987) Conditioned place preference: a parametric analysis using system heroin injection. In Methods of Assessing the Reinforcing Properties of Abused Drugs (Michael A. Bozarth, ED), pp241-273. Springer, New York.
13 Gorelick, D. A., Gardner, E. L. and Xi, Z. X. (2004) Agents in development for the management of cocaine abuse. Drugs 64, 1547-1573.   DOI   ScienceOn
14 Kest, B., Palmese, C. A., Hopkins, E., Adler, M. and Juni, A. (2001) Assessment of acute and chronic morphine dependence in male and female mice. Pharmacol. Biochem. Behav. 70, 149-156.   DOI   ScienceOn
15 Chung, C. S., Wang, J., Wehman, M. and Rhoads, D. E. (2008) Severity of alcohol withdrawal symptoms depends on developmental stage of Long-Evans rats. Pharmacol. Biochem. Behav. 89, 137-144.   DOI
16 Doremus, T. L., Brunell, S. C., Varlinskaya, E. L. and Spear, L. P. (2003) Anxiogenic effects during withdrawal from acute ethanol in adolescent and adult rats. Pharmacol. Biochem. Behav. 75, 411-418.   DOI
17 El-Kadi, A. O. and Sharif, S. I. (1994) The influence of various experimental conditions on the expression of naloxone-induced withdrawal symptoms in mice. Gen. Pharmacol. 25, 1505-1510.   DOI   ScienceOn
18 Koob, G. F. (1999) Drug addiction: the yin and yang of hedonic homeostasis. Neuron 16, 893-896.
19 Koob, G. F. (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol. Sci. 13, 177-184.   DOI   ScienceOn
20 Landry, M. J., Smith, D. E., McDuff, D. R. and Baghman, O. L. (1992) Benzodiazepine dependence and withdrawal: identification and medical management. J. Am. Board Fam. Pract. 5, 167-175.
21 Mansouripour, S. M. and Afshari, R. (2013) Chlordiazepoxide preventive effect on tramadol overdose induced serotonin syndrome evaluated by hunter and radsmski criteria: a clinical trial. Toxicol. Intern. 20, 126-131.   DOI
22 Morris, S. A., Kelso, M. L., Liput, D. J., Mrshall, K. and Nixon (2010) Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence. Alcohol 44, 89-98.   DOI
23 Zhang, H. and Liu, Z. (2013) The investigation of tramadol dependence with no history of substance abuse: a cross-sectional survey of spontaneously reported cases in Guangzhou city, China. Biomed. Res. Int. 2013, 283425.
24 Mucha, R. F., van der Kooy, D., O'Shaughnessy, M. and Bucenieks, P. (1982) Drug reinforcement studied by the use of place conditioning in rat. Brain Res. 243, 91-105.   DOI   ScienceOn
25 Narita, M., Akai, H., Nagumo, Y., Sunagawa, N., Hasebe, K., Nagase, H., Kita, T., Hara, C. and Suzuki, T. (2004) Implications of protein kinase C in the nucleus accumbens in the development of sensitization to methamphetamine in rats. Neuroscience 127, 941-948.   DOI   ScienceOn
26 Nebhinani, N., Singh, S. M. and Gupta, G. (2013) A patient with tramadol dependence and predictable provoked epileptic seizures. Indian J. Psychiatry 55, 293-294.
27 Park, S. H., Wackernuh, R. C. and Stimmel, G. L. (2014) Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressans? J. Pharm. Prac. 27, 71-78.   DOI