# Metabolic Landscape and Cell-Type-Specific Transcriptional Signatures Associated with Dopamine Receptor Activation in the Honeybee Brain

## TL;DR

This study shows that dopamine in honeybees boosts brain energy use in support cells, not neurons, during foraging.

## Contribution

The study reveals cell-type-specific metabolic changes in honeybee brains triggered by dopamine receptor activation.

## Key findings

- Dopamine receptor activation increases brain sugar metabolism, primarily in glial cells.
- Glycolysis and pentose phosphate pathway enzymes are upregulated in glial and neuronal cells.
- Increased energy production is linked to stress byproducts in honeybee brains.

## Abstract

The pollination services provided by honeybees make them vital for global food security. To perform demanding tasks such as foraging, bees must manage their energy efficiently, a process regulated by brain chemicals such as dopamine. However, it is not fully understood how dopamine specifically alters the brain’s energy usage. In this study, we treated honeybees with a substance that activates dopamine receptors and used advanced analysis to examine changes in their brain chemistry and gene activity. We found that dopamine receptor activation coincides with a shift in metabolism, causing the brain to consume more sugar for energy. Crucially, we observed that this energy boost occurs primarily in glial cells—the “support cells” that protect and feed the neurons—rather than in the nerve cells themselves. We also detected chemical markers indicating that this high-energy mode produces stress byproducts. These results suggest that support cells are metabolically active in fueling the honeybee brain during complex behaviors. Understanding these internal energy mechanisms provides new insights into how bees adapt to environmental stress, which is essential for understanding the metabolic constraints that support the demanding task of foraging.

Background: Honeybees sustain vital ecological roles through foraging behavior, which provides pollination services and is likely regulated by dopamine signaling coupled to brain energy metabolism. However, the genetic and metabolic mechanisms underlying this regulation remain unclear. Methods: We treated honeybee workers with the dopamine receptor agonist bromocriptine and employed an integrative approach, combining liquid chromatography–mass spectrometry (LC–MS) metabolomics with single-nucleus RNA sequencing (snRNA-seq). Results: Metabolomics revealed increased levels of N6-carboxymethyllysine (CML) and a coordinated shift in central carbon metabolites, including higher glucose, pyruvate, and lactate within glycolysis, and ribose-5-phosphate in the pentose phosphate pathway (PPP). Integration with transcriptomics showed heterogeneous responses: glial cells exhibited higher glycolysis pathway scores and upregulated hexokinase expression compared to neurons, whereas major PPP enzymes were upregulated in both glial and neuronal subsets. Conclusions: These findings suggest that dopamine receptor activation is associated with altered whole-brain metabolic profiles and concurrent, cell-type-specific upregulation of glycolytic and PPP enzyme genes, particularly in glia. This study characterizes these neuro-metabolic associations, offering insights into the cellular and metabolic basis of foraging behavior in worker bees.