This new research identifies how cocaine changes the configuration of receptors and function in the reward areas of the brain. It adds to the evidence that an increase in glutamate is a key feature of addiction. Some of the medications currently used for alcohol dependence, such as topiramate, baclofen and acamprosate, may work by helping to restore the balance between glutamate and GABA.
Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area
Manuel Mameli, Camilla Bellone, Matthew T C Brown & Christian Lüscher
Nature Neuroscience (2011) 14, 414-416
The manner in which drug-evoked synaptic plasticity affects reward circuits remains largely elusive. We found that cocaine reduced NMDA receptor excitatory postsynaptic currents and inserted GluA2–lacking AMPA receptors in dopamine neurons of mice. Consequently, a stimulation protocol pairing glutamate release with hyperpolarizing current injections further strengthened synapses after cocaine treatment. Our data suggest that early cocaine-evoked plasticity in the ventral tegmental area inverts the rules for activity-dependent plasticity, eventually leading to addictive behavior.