Hypericum perforatum CO2 extract and opioid receptor antagonists act synergistically to reduce ethanol intake in alcohol-preferring rats

BACKGROUND: Hypericum perforatum extracts attenuate ethanol intake in alcohol-preferring rats. The opioid receptor antagonists, naloxone and naltrexone, reduce ethanol intake in rats and humans. The combination of different agents that reduce ethanol intake has been proposed as an approach to the pharmacotherapy of alcoholism. This study evaluated the effect on ethanol intake of the combined administration of a CO2 H. perforatum extract and naloxone or naltrexone in genetically selected Marchigian Sardinian alcohol-preferring rats. METHODS: Ten percent (v/v) ethanol intake was offered 2 hr per day at the beginning of the dark phase of the reverse light-dark cycle. H. perforatum CO2 extract was given intragastrically, 1 hr before access to ethanol. Naloxone or naltrexone was given by intraperitoneal injection 10 min before the extract. RESULTS: H. perforatum CO2 extract reduced ethanol intake at 31 or 125 mg/kg, but not 7 mg/kg. These doses neither modified food or water intake during access to ethanol, nor reduce 0.2% saccharin intake. Naloxone reduced ethanol and food intake at 3 or 5 mg/kg, but not 1 mg/kg. When naloxone 1 mg/kg was combined with the three doses of H. perforatum CO2 extract, the attenuation of ethanol intake was more pronounced than that observed after the administration of the extract alone. Alcohol intake was also significantly reduced by 7 mg/kg of H. perforatum CO2 extract combined with naloxone 1 mg/kg. The combined treatments never modified the rat's locomotor activity nor the simultaneous intake of food, water or 0.2% saccharin. Naltrexone reduced ethanol intake at 1 and 3 mg/kg, but not at 0.5 mg/kg. When naltrexone 0.5 mg/kg was combined with H. perforatum CO2 extract 7 mg/kg, ethanol intake was markedly reduced. CONCLUSIONS: These findings provide evidence that H. perforatum CO2 extract and opiate receptor antagonists act synergistically to induce a pronounced and selective reduction of voluntary ethanol consumption in alcohol-preferring rats.