The role of BDNF/TrkB Signalling in Somatostatin Neurons in Cocaine-Seeking Behaviour

Relapse is the most challenging feature of cocaine addiction. Somatostatin (SST) expressing interneurons are involved in neuronal plasticity and are important in modulating cocaine-seeking behaviour in mice. Since Brain-Derived Neurotrophic Factor and its receptor TrkB drive plasticity, we examined whether TrkB in SST cells is required for extinction of cocaine-seeking using the conditioned place preference (CPP) test. Mice with a heterozygous TrkB knockout restricted in SST neurons acquired cocaine-CPP but failed to extinguish it, indicating that extinction depends on TrkB-mediated neural plasticity in SST neurons. Conversely, activating a light-activable TrkB (optoTrkB (E281A) in infralimbic SST neurons in the prefrontal cortex reduced later relapse of cocaine seeking behaviour. These results show that TrkB signalling in SST interneurons is critical for consolidating extinction and preventing reinstatement of cocaine CPP, highlighting the BDNF/TrkB pathway in SST neurons as a potential therapeutic target.