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Ethanol is oxidized in the brain to acetaldehyde, which can condense with dopamine to generate (R/S)‐salsolinol [(RS)‐SAL]. Racemic salsolinol [(RS)‐SAL] is self‐infused by rats into the posterior ventral tegmental area (VTA) at significantly lower concentrations than those of acetaldehyde, suggesting that (RS)‐SAL is a most active product of ethanol metabolism. Early studies showed that repeated intraperitoneal or intra‐VTA administration of (RS)‐SAL (10 mg/kg) induced conditioned place preference, led to locomotor sensitization and increased voluntary ethanol consumption. In the present study, we separated the (R)‐ and (S)‐enantiomers from a commercial (RS)‐SAL using a high‐performance liquid chromatography with electrochemical detection system fitted with a β‐cyclodextrin‐modified column. We injected (R)‐SAL or (S)‐SAL (30 pmol/1.0 μl) into the VTA of naïve UChB rats bred as alcohol drinkers to study whether one or both SAL enantiomers are responsible for the motivated behavioral effects, sensitization and increase in voluntary ethanol intake. The present results show that repeated administration of (R)‐SAL leads to (1) conditioned place preference; (2) locomotor sensitization; and (3) marked increases in binge‐like ethanol intake. Conversely, (S)‐SAL did not influence any of these parameters. Overall, data indicate that (R)‐SAL stereospecifically induces motivational effects, behavioral sensitization and increases ethanol intake.
Ethanol is oxidized in the brain to acetaldehyde, which can condense with dopamine to generate (R/S)‐salsolinol [(RS)‐SAL]. Behavioral studies in rats have suggested that (RS)‐SAL would be involved in the rewarding/reinforcing effects of ethanol. However, it is not known whether the (RS)‐SAL effects are due to one or both enantiomers. The present study shows that (R)‐salsolinol [(R)‐SAL] injected into the ventral tegmental area (VTA) (at days 1, 3, 5 and 13; arrows) greatly produces binge‐like ethanol drinking (reaching 3 g ethanol intake/kg/60 minutes) in ethanol‐naïve rats. Conversely, (S)‐SAL was fully inactive in the same model. Also, administration of (R)‐SAL, but not of (S)‐SAL, results in conditioned place preference and marked behavioral (locomotor) sensitization. The present studies suggest that (R)‐SAL generates long‐lasting effects akin to those that have been reported following chronic ethanol intake, and might be considered a mediator of ethanol effects.