Methylnaltrexone attenuates taste aversion conditioned by low-dose ethanol

Previous research has shown that activation of a subset of peripheral opioid receptors located in the gut produce aversive effects as measured in the place and taste conditioning (CTA) paradigms. Endogenous opioid activity and tetrahydroisoquinolines (TIQs) are stimulated or formed after ethanol (EtOH) administration and both are known to activate opioid receptors. We therefore examined the hypothesis that a portion of the aversive effects of EtOH may be mediated through peripheral opioid receptors, activated by EtOH-induced opioids or TIQs. EtOH CTAs were slightly attenuated when animals were pretreated with the putative peripheral opioid receptor antagonist methylnaltrexone. By itself MNTX did not condition a taste preference or aversion. However, blood EtOH levels (BELs) in animals pretreated with MNTX were lower than those of saline-pretreated subjects, an effect that just reached statistical significance and was not present at specific EtOH doses. The results indicate that a portion of the aversive conditioning effects of EtOH (using a two-bottle CTA paradigm) may be receptor-mediated effects, exerted by an action on peripheral opioid receptors, but the specific mechanism of attenuation is unclear.