Revisiting the controversial role of salsolinol in the neurobiological effects of ethanol: Old and new vistas

The possible involvement of salsolinol (Sal), an endogenous condensation product of ACD (the first metabolite of ethanol) and dopamine, in the neurochemical basis underlying ethanol action has been repeatedly suggested although it has not been unequivocally established, still being a controversial matter of debate. The main goal of this review is to evaluate the presumed contribution of Sal to ethanol effects summarizing the reported data since the discovery in the 1970s of Sal formation in vitro during ethanol metabolism until the more recent studies characterizing its behavioral and neurochemical effects. Towards this end, we first analyze the production and detection of Sal, in different brain areas, in basal conditions and after alcohol consumption, highlighting its presence in regions especially relevant in regulating ethanol-drinking behaviour and the importance of the newly developed methods to differentiate both enantiomers of Sal which could help to explain some previous negative findings. Afterwards, we review the behavioral and neurochemical studies. Finally, we present and discuss the previous and current enunciated mechanisms of action of Sal in the CNS.