Lastly, the authors studied dopaminergic, cholinergic, and cannabinoid receptor activity to explain how handling and NORT changed passive avoidance response, since there is evidence that the interaction of these systems modulates fear expression. Despite robust evidence that dopaminergic signaling plays a role in regulating fear response, rotigotine, a dopamine agonist, had no effect on G protein-coupled receptor-mediated activity. The authors instead found that cannabinoid signaling is involved in these behavioral modulations: rats who were not subjected to handling or NORT prior to performing the passive avoidance test displayed the highest cannabinoid activity in the nucleus basalis magnocellularis (NBM), as well as the lowest percentage of freezing time (Figure 2).
Additionally, the authors found increased cholinergic signaling in rats who had not been exposed to handling or NORT, but no direct correlation was found between cholinergic activity in the NBM and freezing time. However, since increased cholinergic signaling was observed in the same region as increased cannabinoid signaling, the authors suggested that there may be crosstalk between these systems in the regulation of these fear extinction and expression processes.