Pro-Cognitive Effect of Royal Jelly Is Linked with Increased Burst Activity of Mesocorticolimbic Dopaminergic Neurons

Background: Royal jelly is a protein-rich honeybee secretion that is used in the nutrition of larvae and adult queens. Previous studies have reported that royal jelly had induced pro-cognitive, anxiolytic, and antidepressant-like effects in laboratory rats. Since serotonin (5-HT), noradrenaline, and dopamine play an important role in the control of several mental functions, changes in the excitability of monoaminergic neurons may be involved in the mechanisms of the behavioral and neurochemical effects of royal jelly. The present study aimed to test this hypothesis. Methods: Adult male Wistar rats were treated with royal jelly for two weeks. Thereafter, their cognitive performance was evaluated using the novel object recognition (NOR) test. The excitability of monoaminergic neurons was assessed using in vivo single-unit extracellular electrophysiology. Results: We found that rats treated with royal jelly had a higher recognition index in the NOR test and a higher burst activity of dopaminergic neurons of the ventral tegmental area (VTA) compared to the vehicle-treated controls. The firing activities of 5-HT neurons of the dorsal raphe nucleus (DRN) and the noradrenergic neurons of the locus coeruleus (LC) were not altered. Conclusions: We conclude that the pro-cognitive effect of royal jelly is mediated, at least in part, by mechanisms involving the excitability of mesolimbic dopaminergic neurons. The present findings encourage further research towards the improvement of the safety and efficacy of currently available therapies for cognitive dysfunction.