Annika Ruppert

The molecular target of synthetic opioids, such as fentanyl, is the mu-opioid receptor (MOR), which is highly expressed in the nucleus accumbens (NAc), a region of the striatum that is important for reward. While the main neurons of the NAc are the medium spiny neurons, local GABAergic interneurons are known to provide robust inhibitory modulation within the NAc. Little is known about MOR’s functional expression in a subset of these interneurons, the somatostatin-expressing (SST) interneurons. I tested the hypothesis that SST-MOR expression in the NAc enforces locomotor sensitization, a classic behavior that occurs with drugs of abuse. To test this hypothesis, I used a transgenic mouse line that expresses Flp recombinase in SST cells and carries LoxP sites around the MOR gene. This allowed us to excise MOR from the SSTs in the NAc upon viral delivery of a Flp-dependent Cre recombinase. To assess locomotor sensitization, I administered fentanyl (0.4mg/kg) daily for 7 days, and measured locomotor activity after injection on days 1 and 7. A two-way ANOVA revealed no significant difference of distance traveled between Flp+ (n=14) and Flp- (n=15) animals. This result suggests that locomotor sensitization is not reliant on the MOR expression in accumbal SSTs. However, this does not rule out effects of reward-based behaviors like conditioned place preference, as future experiments will test. These results are important in understanding how SST neurons contribute to the behavioral consequences of opioid administration, and this could lead to a novel therapeutic target for opioid-use disorders.