Post-trial low dose apomorphine prevents the development of morphine sensitization

Abstract

The development of sensitization is one of the hallmarks of addictive drugs. Consistent with this relationship many studies have demonstrated that the highly addictive opioid agonist morphine induces sensitization effects. In this study, we administered morphine (10 mg/kg) (MOR) to induce sensitization. In that sensitization is considered to involve associative processes and that dopamine activity is an important contributor to learning and memory processes, we administered a dopamine inhibitory treatment using apomorphine (0.05 mg/kg) (APO) during memory consolidation following a morphine sensitization treatment protocol. Seemingly, a decrease in dopamine activity during consolidation would impair the salience of the association of the morphine response with the contextual cues during consolidation and interfere with the development of morphine sensitization. In two separate experiments, MOR or vehicle (VEH) were administered pre-trial and either VEH or APO were administered post-trial over 5 and 10 days of treatment, respectively. In both the 5 and 10 drug treatment sessions post-trial experiments, MOR groups given VEH immediately post-trial exhibited strong sensitization effects. These sensitization effects were substantially attenuated in the MOR groups given APO immediately post-trial but not in the MOR groups given APO after a 15 min. post-trial delay. In subsequent conditioning and sensitization challenge tests, the MOR groups that had been given APO immediately post-trial exhibited diminished sensitization and conditioned responses relative to MOR groups that had received VEH or APO delayed post-trial. This MOR-APO interaction effect was unique in that it occurred post-trial so that it was only expressed in a pre-trial test in which only MOR was administered. Seemingly, the inhibitory dopamine effect of APO was incorporated into memory during the post-trial consolidation process suggesting that drug/drug interactions can occur during consolidation.

Keywords: Addiction; Apomorphine; Behavioral sensitization; Conditioning; Consolidation; Morphine.