摘要Areca nut is the basic ingredient of betel quid,which is chewed by hundreds of millions of people in South-Eastern Asia.Chewing of areca nut has been associated with oral cancers potentially due to its specific alkaloids,among which arecoline constitutes about 90％of total fraction.Being the world's fourth most commonly used psychoactive substance,arecoline evokes stimulation,addiction,and other direct neurological effects,while its misuse correlates to neurotoxic effects.However,what might underlie its neurotoxic mechanisms has been poorly documented.The brain is encoded by a complex network of neuronal and glial cell types,and neurotoxicity of hazardous compounds present transcriptional heterogeneity.Recently,the eusocial bumblebee has been used as a model for studying brain effects,with sophisticated cognitive capability and precisely measured brain architecture.Here,we decipher cell-type-specific mental risks to arecoline using bumblebees.Arecoline induced locomotor hyperactivity and cognitive impairment.Single nucleus RNA sequencing(snRNA-seq)unearthed arecoline-induced cell-specific responses,primarily targeted on Kenyon cells(KC).Moreover,high-dose arecoline induced distinctive cell responses among KC subtypes,particularly class Ⅰ large Kenyon cell(lKC),leading to DNA damage,excitatory/inhibitory(E/I)imbalance,and calcium dyshomeostasis,which potentially resulted in cognitive impairment.Given arecoline's popularity and growing exposure risks to humans,neurological health risks of areca nut warrant serious consideration.