Acamprosate reduces ethanol intake in the rat by a combined action of different drug components

Abstract

Abstract Alcohol misuse accounts for a sizeable proportion of the global burden of disease, and Campral® (acamprosate; calcium-bis-(N-acetylhomotaurinate)) is widely used as relapse prevention therapy. The mechanism underlying its effect has in some studies been attributed to the calcium moiety and not to the N-acetylhomotaurine part of the compound. We recently suggested that the dopamine elevating effect of acamprosate is mediated both by N-acetylhomotaurine and calcium in a glycine receptor dependent manner. Here we aimed to explore, by means of in vivo microdialysis, if systemic administration of the sodium salt of N-acetylhomotaurine (sodium acamprosate; 200 mg/kg, i.p.) enhanced the effects of calcium chloride (CaCl2; 73.5 mg/kg, i.p.) on nucleus accumbens (nAc) dopamine and/or taurine levels in male Wistar rats. In addition, we investigated if N-acetylhomotaurine potentiates the ethanol-intake reducing effect of CaCl2 in a two-bottle choice voluntary ethanol consumption model followed by an alcohol deprivation effect paradigm. Systemic administration of regular acamprosate, sodium acamprosate or the combination of CaCl2 and sodium acamprosate significantly increased extracellular dopamine and taurine levels in the nAc. CaCl2 alone instantly increased dopamine but the effect did not sustain throughout the entire measured time period and taurine levels were not altered. Ethanol intake was significantly reduced by systemic administration of CaCl2, but the addition of sodium acamprosate prolonged the calcium-induced reduction of ethanol intake. Neither treatment suppressed the alcohol deprivation effect. The data presented suggest that CaCl2 and N-acetylhomotaurinate act in concert both regarding elevation of extracellular nAc dopamine levels and in reducing ethanol intake.