Alternative treatment for alcohol-dependence in alcohol preferring (P) rats

Alcoholism is a serious public health problem. Therefore, identification of a therapeutic agent that selectively reduces alcohol consumption and the withdrawal symptoms is a major goal of alcoholism research. In this thesis study we describe the anti-alcoholism potency of kudzu root extract (KdR) and its key isoflavone, Puerarin (PU) in alcohol preferring (P) rats. (1) P rats drank 7 to 10 g alcohol/kg/day with blood alcohol values ranging from 16 to 24 mg/dl. Water intake was inversely related to the amount of alcohol consumed. Alcohol withdrawal after 69 days of alcohol drinking caused withdrawal symptoms. The 0.5 g/kg KdR dose caused 50% reduction in alcohol consumption, abolished the withdrawal symptoms, but did not affect blood alcohol levels. The higher kudzu root extract doses did not further reduce alcohol consumption. The liver samples contained mostly PU and a trace amount of daidzein (DE), while plasma and brain samples obtained from KdR fed or alcohol and KdR fed rats did not contain any of the KdR isoflavones. Thus, KdR isoflavones suppressed alcohol drinking and withdrawal symptoms without entering the brain, possibly through indirect systemic effects. (2) PU accounted for 80% of total isoflavones in KdR. This study suggests differences in the bio-availability of isoflavones when they are ingested as purified compounds than as crude plant extract. (3) A daily 50 mg/kg dose of PU caused approximately 50% suppression in alcohol intake in P rats receiving water and 15% ethanol. Alcohol ingestion gradually returned to the control level despite consistent PU intake. PU suppressed the severity of alcohol withdrawal symptoms. Liver samples obtained from PU-fed P rats contained 20–30 μg/g PU. Plasma or brain samples did not contain PU. An absence of PU in plasma and brain indicate the possibility that some non-specific mechanism may be involved in the anti-alcoholism effects of PU in P rats.; The present observation that KdR or PU suppressed alcohol ingestion and the withdrawal symptoms without accumulating in blood or the brain suggests that isoflavone accumulation in liver causes some, yet unidentified, systemic changes that may be involved in the therapeutic effects of KdR and/or PU.