Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning

Drugs of abuse alter synaptic connections in the ‘reward circuit’ of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation (LTP) in the ventral tegmental area (VTA), and is recruited to the synaptic membrane of excitatory inputs onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a significant reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction.