Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABA(B) receptor

• Published in: European journal of pharmacology 2008-06, Vol.587 (1-3), p.124
• Main Authors: Jang, Eun Young, Choe, Eun Sang, Hwang, Meeyul, Kim, Sang Chan, Lee, Jong Rok, Kim, Sang Geon, Jeon, Jae-Pil, Buono, Russell J, Yang, Chae Ha
• Format: Article
• Language: English
• Subjects: Animals; Chalcones - antagonists & inhibitors; Chalcones - pharmacology; Cocaine - antagonists & inhibitors; Cocaine - pharmacology; Dopamine - metabolism; Dopamine Uptake Inhibitors - antagonists & inhibitors; Dopamine Uptake Inhibitors - pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Extracellular Space - drug effects; Extracellular Space - metabolism; Glycyrrhiza - chemistry; Male; Microdialysis; Morpholines - pharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Receptors, GABA-B - drug effects; Receptors, GABA-B - metabolism
• ISSN: 0014-2999
• DOI: 10.1016/j.ejphar.2008.03.054

Glycyrrhizae radix (licorice) comprises a variety of flavonoids as major constituents including isoliquiritigenin, liquiritin, liquiritigenin, and glycyrrihizin. It has shown various biological activities such as anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to drug addiction, we carried out a study on the effect of G. radix and its active component, isoliquiritigenin, on acute cocaine-induced extracellular dopamine release in moving rats. Male Sprague-Dawley rats were orally administered with methanolic extracts of G. radix or isoliquiritigenin 1 h prior to an injection of cocaine (20 mg/kg, intraperitoneal (i.p.)). Extracellular dopamine was measured by in vivo microdialysis. Extract of G. radix and isoliquiritigenin inhibited cocaine-induced extracellular dopamine level in the nucleus accumbens by dose-dependent manner. Inhibition of dopamine release by isoliquiritigenin resulted in attenuation of the expression of c-Fos, an immediately early gene induced by cocaine. Effect of isoliquiritigenin was completely prevented by a GABA(B) receptor antagonist. Thus, these results showed that G. radix and isoliquiritigenin inhibit cocaine-induced dopamine release by modulating GABA(B) receptor, suggesting that isoliquiritigenin might be effective in blocking the reinforcing effects of cocaine.