Characterization of the discriminative stimulus effects of the delta‐opioid receptor agonist, SNC80, in rats

Abstract

Delta opioid receptor (DOR) agonists produce antihyperalgesia and antidepressant‐like effects, but they also induce convulsions limiting their clinical development. Recently, some work has shown that not all DOR agonists produce convulsions in rodents. Therefore, the current study aimed to further evaluate the pharmacological properties of these DOR ligands using a drug discrimination paradigm in male Sprague‐Dawley rats. The drug discrimination assay is useful for identifying compounds with similar interoceptive properties and evaluating the pharmacological activity of ligands in vivo. For this study, rats were trained to discriminate 3.2 mg/kg SNC80 from saline on a fixed ratio (FR) 10 schedule of reinforcement in a food‐reinforced, drug discrimination paradigm. Substitution patterns with purported DOR agonists AZD2327, DPI287, KNT127, and MMP2200 were evaluated as well as profiles of antagonism following pretreatment with naltrindole. Agonists that are structurally similar to SNC80, AZD2327 and DPI287, generalized to SNC80 while structurally unrelated agonists, KNT127 and MMP2200, did not. Morphine, ketamine, desipramine, cocaine, and nicotine failed to generalize to SNC80 up to doses that suppressed responding; however, amphetamine produced partial generalization to the discriminative stimulus effects of SNC80. The DOR antagonist naltrindole produced parallel, rightward shifts in the SNC80 dose effect curve. Overall, these data suggest that interoceptive effects differ among DOR agonists, which may contribute to their distinct profiles of behavioral activity and potentially diverse mechanisms of action. Future studies will further probe the pharmacological and/or signaling mechanisms that differentiate the behavioral effects of DOR agonists.Support or Funding InformationThis work is supported in part by R01 DA042092 (EMJ) and the IRPs of NIDA and NIAAA (KCR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.