Abstract: To investigate the role and molecular regulation mechanism of dopamine signaling pathway in forgetting, the key components of this pathway were screened using theCaenorhabditis elegansfood-butanone positive associative learning model, including tyrosine hydroxylase (CAT-2), dopamine transporter (DAT-1), dopamine receptor (DOP-1/2/3/4), G protein, cAMP and PLC pathways. The results showed that mutations incat-2or treatment with 6-OHDA disrupted normal dopamine signal transmission, leading to a notable decline in the worm’s learning and memory retention abilities. Mutations indat-1impeded dopamine reuptake, resulting in accelerated forgetting.dop-1mutant animals exhibited memory retention deficits, whiledop-2,dop-3, anddop-4mutants showed no significant difference from the control group. Among the screened G proteins (GSA-1, GOA-1, EGL-30), onlygsa-1mutation accelerated forgetting. Additionally, key members of the cAMP and PLC pathways were examined, revealing that mutations inkin-2(PKA) within the cAMP pathway expedited forgetting. The findings suggested that dopamine played a role in the regulation of forgetting inC. elegans, potentially acting through the DOP-1/GSA-1/PKA pathway. This study provided a theoretical foundation for understanding the role of dopamine in forgetting and offers insights into the comparison of dopamine systems across species evolution.

Key words: dopamine;Caenorhabditis elegans, the food-butanone positive association learning model, mutant, cAMP pathway