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 measur ed in the place and taste conditioning (CTA) paradigms. Endogenous opi oid activity and tetrahydroisoquinolines (TIQs) are stimulated or form ed 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 opi oid receptors, activated by EtOH-induced opioids or TIQs. EtOH CTAs we re 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 o f saline-pretreated subjects, an effect that just reached statistical significance and was not present at specific EtOH doses. The results i ndicate that a portion of the aversive conditioning effects of EtOH (u sing a two-bottle CTA paradigm) may be receptor-mediated effects, exer ted by an action on peripheral opioid receptors, but the specific mech anism of attenuation is unclear. (C) 1998 Elsevier Science Inc.