Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABA(B) receptor.
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.
Jang
Eun Young
EY
Department of Physiology, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, South Korea.
Choe
Eun Sang
ES
Hwang
Meeyul
M
Kim
Sang Chan
SC
Lee
Jong Rok
JR
Kim
Sang Geon
SG
Jeon
Jae-Pil
JP
Buono
Russell J
RJ
Yang
Chae Ha
CH
D000818:Animals; D047188:Chalcones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006035:Glycyrrhiza / Q000737:chemistry; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D047188:Chalcones; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D009025:Morpholines; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D018080:Receptors, GABA-B; C040920:isoliquiritigenin; D003042:Cocaine; D004298:Dopamine