Comparison of Morphine’s and Fentanyl’s Interoceptive Effects in Rats through Occasion Setting in a Discriminative Goal Tracking Model

The increased prevalence of recreational synthetic opioids and the COVID-19 pandemic have led to an increase in opioid overdose deaths. The interceptive effects of opioids lead to a high misuse potential, and this can be studied utilizing a discriminative goal tracking (DGT) model. However, previous research has been limited to morphine. The objective of the current study was to determine the interoceptive effects of fentanyl, a synthetic opioid, in comparison to morphine utilizing an occasion setting model. Sprague-Dawley rats were split evenly by gender into feature positive (FP) and feature negative (FN) groups. Morphine served as the feature and a 15-sec light cue served as the target. Rats received morphine (3.73 mg/kg) or saline injections 5-min prior to each session. FP rats received the unconditioned stimulus (US), sucrose, when the feature and the target were both present, whereas FN rats received the US when only the target was present. Rats then underwent dose generalization testing with five morphine doses and seven fentanyl doses. Naloxone antagonism tests were performed for each drug after each rat’s completion of the respective dose generalization curve. The FP group acquired drug discrimination quicker than the FN group. The lowest morphine dose discriminable from saline was 1.0 mg/kg for the FP group and 3.73 mg/kg for the FN group. The lowest fentanyl dose discriminable from saline was 3.49 µg/kg for the FP group and 8.9 µg/kg for the FN group. Naloxone administered with 3.73 mg/kg morphine or 8.9 µg/kg fentanyl antagonized the drug’s interoceptive effects so that the presence of the drug was no longer discriminable from saline. Fentanyl produced similar interoceptive effects as morphine but at a significantly smaller dose. This highlights the importance of the continued study of the interoceptive effects of synthetic opioids which will better help combat the current opioid epidemic