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Evidence-Based Complementary and Alternative Medicine
Volume 6, Issue 1, Pages 85-90
Original Article

Inhibitory Effects of Coptidis rhizoma and Berberine on Cocaine-Induced Sensitization

1Department of Neurobiology/Division of Neuroscience, Children's Hospital and Harvard Medical School, Boston, USA
2Department of Physiology, College of Oriental Medicine, Daegu Haany University, Republic of Korea
3Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Republic of Korea
4Division of Biological Sciences, Pusan National University, Republic of Korea
5Department of Integrative Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137-701, Republic of Korea

Received 11 May 2006; Accepted 26 April 2007

Copyright © 2009 Bombi Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Substantial evidence suggests that the behavioral and reinforcing effects of cocaine can be mediated by the central dopaminergic systems. Repeated injections of cocaine produce an increase in locomotor activity and the expression of tyrosine hydroxylase (TH) in the main dopaminergic areas. Protoberberine alkaloids affect neuronal functions. Coptidis rhizoma (CR) and its main compound, berberine (BER) reduced the dopamine content in the central nervous system. In order to investigate the effects of CR or BER on the repeated cocaine-induced neuronal and behavioral alterations, we examined the influence of CR or BER on the repeated cocaine-induced locomotor activity and the expression of TH in the brain by using immunohistochemistry. Male SD rats were given repeated injections of saline or cocaine hydrochloride (15 mg/kg, i.p. for 10 consecutive days) followed by one challenge injection on the 4th day after the last daily injection. Cocaine challenge (15 mg/kg, i.p) produced a larger increase in locomotor activity and expression of TH in the central dopaminergic areas. Pretreatment with CR (50, 100, 200 and 400 mg/kg, p.o.) and BER (200 mg/kg, p.o.) 30 min before the daily injections of cocaine significantly inhibited the cocaine-induced locomotor activity as well as TH expression in the central dopaminergic areas. Our data demonstrate that the inhibitory effects of CR and BER on the repeated cocaine-induced locomotor activity were closely associated with the reduction of dopamine biosynthesis and post-synaptic neuronal activity. These results suggest that CR and BER may be effective for inhibiting the behavioral effects of cocaine by possibly modulating the central dopaminergic system.