Quaternary naloxone enhances acquisition of a discriminated Y-maze escape and a one-way active avoidance task in mice

Methylnaloxonium, a quaternary form of naloxone that does not readily cross the blood brain barrier, enhanced acquisition of a Y-maze shock escape and a one-way active avoidance response in mice in doses that did not affect shock-induced locomotor activity in an open field. Since methylnaloxonium is a opioid antagonist, it is likely that the observed enhancement of learning is due to the drug preventing endogenous opioid peptides from reaching their receptors. The results therefore suggest that manipulation of peripheral opioid systems alters the strength of a conditioned response.