Fentanyl is a powerful painkiller that elicits euphoria and positive reinforcement1. Fentanyl also leads to dependence, defined by the aversive withdrawal syndrome, which fuels negative reinforcement (i.e., individuals take the drug to avoid withdrawal)2,3. Positive and negative reinforcement maintain consumption, which leads to addiction in a third of users, the highest fraction of all drugs of abuse4. Among the opioid receptors (ORs), µORs are key5, yet the induction loci of circuit adaptations eventually leading to addiction remain elusive. Here, we injected mice with fentanyl to acutely inhibit GABA neurons in the ventral tegmental area (VTA), causing disinhibition of dopamine (DA) neurons, eventually increasing DA in the nucleus accumbens (NAc). While removing µORs from the VTA abolished DA transients and positive reinforcement, withdrawal remained unchanged. We identified µORs-expressing neurons in the central amygdala (CeA) whose activity was enhanced during withdrawal. Removing µORs in these cells eliminated aversive symptoms, suggesting they mediate negative reinforcement. Thus, mice learned to press a lever to pause optogenetic stimulation of µORs-expressing CeA neurons. Our study parses the neuronal populations triggering positive and negative reinforcement in the VTA and CeA, respectively. We lay out the circuit organization to develop interventions reducing fentanyl addiction and facilitating rehabilitation.