FAILURE OF AN OPIATE TO PROTECT MICE AGAINST NALOXONE-PRECIPITATED WITHDRAWAL

¹ Department of Pharmacology, Stanford University, Stanford, California

Mice were made dependent upon the opiate narcotic, levorphanol, by repeated injections of a fixed dose at a four-or eight-hour interval. The degree of dependence was measured by determining the ED5O of naloxone for eliciting jumping activity. After dependence was established, on either schedule, the greatly increased plasma and brain levels of the agonist (levorphanol) after an injection did not cause any increase in the ED5O of the antagonist (naloxone). The behavior of antagonists in blocking primary opiate effects is competitive. In contrast, the results reported here indicate that even a large increase of levorphanol concentration in brain does not protect against naloxone precipitated withdrawal.