Bee venom enhances dopaminergic function and behavioral recovery in a murine model of Parkinson's disease

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons, leading to motor dysfunction and cognitive impairment. Although levodopa (l-DOPA)/carbidopa remains the gold standard therapy for PD, its efficacy declines over time, highlighting the need for adjuvant strategies that improve functional outcomes. This study evaluated whether freeze-dried bee venom (BV) enhances the behavioral effects of l-DOPA/carbidopa in a murine model of PD.

Adult male mice (age: 3.0-3.5 months) were randomly assigned using a computer-generated randomization sequence to the following experimental groups: SHAM, animals that were injected with saline in the dorsomedial striatum (STR) (n = 6); 6-hydroxydopamine (6-OHDA) lesion, animals that received an injection of 6-OHDA in the STR (n = 7); l-DOPA/carbidopa, lesioned animals that were treated with l-DOPA/carbidopa from day 13 (D13) to day 30 (D30) after the lesion (n = 7); and l-DOPA/carbidopa + BV, lesioned animals treated with a combination of l-DOPA/carbidopa and BV from D13 to D30 after the lesion (n = 7). Motor asymmetry and paw dragging were assessed using the cylinder test, and lateralized function was assessed using the corridor test. Cognitive performance was evaluated with the novel object recognition (NOR) test. Behavioral data were analyzed using the Kruskal-Wallis test followed by Dunn's post hoc comparisons.

Compared with 6-OHDA treatment, the combined treatment with BV and l-DOPA/carbidopa significantly improved forelimb motor symmetry (H = 15.16, p = 0.001) and reduced contralateral paw dragging (H = 19.91, p < 0.001). In the corridor test, compared with l-DOPA/carbidopa alone, BV cotreatment increased the retrieval index (H = 16.43, p < 0.001). Moreover, BV prevented 6-OHDA-induced cognitive impairment in the NOR test, restoring the discrimination index to levels comparable to those of the SHAM group (H = 17.48, p < 0.001).

These findings provide behavioral evidence that BV may serve as a promising adjuvant to l-DOPA/carbidopa, improving both motor and cognitive outcomes in a mouse model of PD and supporting further investigation in studies incorporating histological and molecular endpoints.