eCAM Advance Access published online on October 18, 2007
eCAM, doi:10.1093/ecam/nem070
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, Daegu, 3Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Suwon, 4Division of Biological Sciences, Pusan National University, Pusan and 5Department of Integrative Medicine, College of Medicine, The Catholic University of Korea, South Korea
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.
Keywords: cocaine – berberine – Coptidis rhizome – locomotor activity – tyrosine hydroxylase – ventral tegmental area
For reprints and all correspondence: Insop Shim, PhD, Department of Integrative Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137-701, South Korea. Tel: 82-2-590-2971; Fax: 82-2-592-6359; E-mail: ishim{at}catholic.ac.kr
Received May 11, 2006; accepted April 26, 2007