Cocaine Experience Controls Bidirectional Synaptic Plasticity in the Nucleus Accumbens

• Published in: The Journal of neuroscience 2007-07, Vol.27 (30), p.7921-7928
• Main Authors: Kourrich, Said, Rothwell, Patrick E, Klug, Jason R, Thomas, Mark J
• Format: Article
• Language: English
• Subjects: Animals; Cocaine - administration & dosage; Cocaine-Related Disorders - physiopathology; Cocaine-Related Disorders - psychology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Male; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Motor Activity - physiology; Nerve Net - drug effects; Nerve Net - physiology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Nucleus Accumbens - drug effects; Nucleus Accumbens - physiology; Synapses - drug effects; Synapses - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1859-07.2007

Plasticity of glutamatergic synapses is a fundamental mechanism through which experience changes neural function to impact future behavior. In animal models of addiction, glutamatergic signaling in the nucleus accumbens (NAc) exerts powerful control over drug-seeking behavior. However, little is known about whether, how or when experience with drugs may trigger synaptic plasticity in this key nucleus. Using whole-cell synaptic physiology in NAc brain slices, we demonstrate that a progression of bidirectional changes in glutamatergic synaptic strength occurs after repeated in vivo exposure to cocaine. During a protracted drug-free period, NAc neurons from cocaine-experienced mice develop a robust potentiation of AMPAR-mediated synaptic transmission. However, a single re-exposure to cocaine during extended withdrawal becomes a potent stimulus for synaptic depression, abruptly reversing the initial potentiation. These enduring modifications in AMPAR-mediated responses and plasticity may provide a neural substrate for disrupted processing of drug-related stimuli in drug-experienced individuals.