Cocaine addiction is a highly debilitating condition consisting of compulsive self-administration and seek for the substance of abuse, and its most challenging feature is the high rate of relapse. Addiction and relapse share similarities with neural plasticity which acts through the Brain-Derived Neurotrophic Factor and its receptor TrkB. Somatostatin (SST) expressing interneurons are involved in neuronal plasticity and are important in modulating cocaine-seeking behaviour in mice. We tested the role of TrkB in Somatostatin (SST)-expressing neurons in the extinction of cocaine-seeking behaviour, using mice in which TrkB has been knocked out specifically in SST neurons. We have observed that in these mice, once a cocaine-conditioned place preference is acquired, its extinction through seven days of extinction training is impaired, showing how this process relies on neural plasticity in SST neurons. When we promoted plasticity during extinction training using a light-activable TrkB in SST neurons in the prefrontal cortex of cocaine-conditioned mice, relapse of cocaine-seeking was prevented. Our data identify the critical role of TrkB-mediated plasticity within SST neurons in the extinction of and relapse to cocaine addiction.