Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine

A compelling model of experience-dependent plasticity is the long-lasting s ensitization to the locomotor stimulatory effects of drugs of abuse. Adapta tions in the nucleus accumbens (NAc), a component of the mesolimbic dopamin e system, are thought to contribute to this behavioral change. Here we exam ine excitatory synaptic transmission in NAc slices prepared from animals di splaying sensitization 10-14 days after repeated in vivo cocaine exposure. The ratio of AMPA (alpha -amino-3-hydroxy-5-methyl-4- isoxazole propionic a cid) receptor- to NMDA (N-methyl-D-aspartate) receptor-mediated excitatory postsynaptic currents (EPSCs) was decreased at synapses made by prefrontal cortical afferents onto medium spiny neurons in the shell of the NAc. The a mplitude of miniature EPSCs at these synapses also was decreased, as was th e magnitude of long-term depression. These data suggest that chronic in viv o administration of cocaine elicits a long-lasting depression of excitatory synaptic transmission in the NAc, a change that may contribute to behavior al sensitization and addiction.