Over half of all smokers relapse within the first 72h of a quit attempt, with early withdrawal symptoms during this period being the most highly cited cause for relapse. Recent work from our lab shows that nicotine abstinence results in a pro-inflammatory cellular environment in the nucleus accumbens, a key brain region associated with both drug dependency and withdrawal phenotypes. This presentation will highlight microglial mechanisms underlying these inflammatory effects and how multi-cellular communication impacts the transcriptomic, functional, and behavioral phenomena defining early nicotine withdrawal.