Aim: Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse.
Methods: Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect.
Results: In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion.
Conclusion: BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.