Comparison of the effects of the selective serotonin-reuptake inhibitors fluoxetine, paroxetine, citalopram and fluvoxamine in alcohol-preferring cAArats

Clinical studies indicate that selective serotonin-reuptake inhibitors (SSR Is) may decrease alcohol intake and craving in particular subgroups of alco holics. The aim of the present study was to compare the behavioral profile of various SSRIs in alcohol-preferring cAA rats, a genetic model of alcohol ism. The effects of acute IP administration of fluoxetine (doses in mg/kg 1 -10), citalopram (3-30), fluvoxamine (3-30) and paroxetine (1-10) on ethano l (EtOH) intake and preference, as well as food and total fluid intake, wer e determined in a 12-h access, water vs. 10% v/v EtOH two-bottle choice par adigm. Each compound reduced EtOH intake [Minimal Effective Doses (MEDs) 5, 10, 30 and 1 mg/kg for fluoxetine, citalopram, fluvoxamine, and paroxetine , respectively]. The degree of selectivity, that is, the extent to which re ductions in EtOH intake could be separated from reductions in food and/or t otal fluid intake varied across the compounds. Thus, whereas EtOH intake wa s more markedly affected than food intake by fluoxetine, both parameters we re equally affected by citalopram, and food intake was more markedly affect ed than EtOH intake by fluvoxamine and paroxetine. The anti-alcohol effect also differed with respect to specificity, that is, the degree to which eff ects on EtOH intake coincided with effects on EtOH preference. Whereas fluo xetine showed the highest level of specificity, followed by citalopram and fluvoxamine, the effect of paroxetine was nonspecific. The observed variati on in the degree of selectivity and specificity of the anti-alcohol effect of SSRIs suggests that reductions in EtOH intake are not merely a consequen ce of a general suppressive effect on consummatory behavior. It is hypothes ized that differences between the behavioral profiles of these compounds re flect a differential involvement of 5-HT receptor subtypes. (C) 1999 Elsevi er Science Inc. All rights reserved.