Synaptic adaptations in the nucleus accumbens caused by experiences linked to relapse

Background: Excitatory synaptic transmission in the nucleus accumbens (NAc) regulates the reinstatement of drug seeking, an animal model of relapse in human drug addicts. However, the functional adaptations at NAc synapses that mediate reinstatement are not clearly understood. Methods: We assessed the behavioral responses of mice to cocaine administration by measuring locomotor stimulation and the acquisition, extinction, and reinstatement of conditioned place preference. Synaptic function was then examined by preparing acute brain slices and performing whole cell voltage-clamp recordings from individual medium spiny neurons in the NAc shell. Results: We find that reduced excitatory synaptic strength in the NAc shell is a common functional adaptation induced by multiple experiences known to cause reinstatement, including stress and drug re-exposure. The same synaptic adaptation is observed shortly after reinstatement of conditioned place preference by a cocaine priming injection. Conclusions: This common synaptic modification associated with stress, drug re-exposure, and reinstatement defines a potential synaptic gateway to relapse.