Chronic cocaine treatment is associated with changes in dendritic spines in the nucleus accumbens, but it is unknown if this neuroplasticity alters the effect of a subsequent cocaine injection on spine morphology and protein content. Three weeks following daily cocaine or saline administration, neurons in the accumbens were filled with the lipophillic dye, DiI. While daily cocaine pretreatment did not alter spine density compared to daily saline, there was a shift from smaller to larger diameter spines. During the first two hours following an acute cocaine challenge, a bidirectional change in spine head diameter and increase in spine density was measured in daily cocaine-pretreated animals. In contrast, no change in spine diameter or density was elicited by a cocaine challenge in daily saline animals during the first two hours after injection. However, spine density was elevated at six hours after a cocaine challenge in daily saline-pretreated animals. The time-dependent profile of proteins in the postsynaptic density subfraction elicited by a cocaine challenge in daily cocaine-pretreated subjects indicated that the changes in spine diameter and density were associated with a deteriorating actin cytoskeleton and a reduction in glutamate signaling-related proteins. Correspondingly, the amplitude of field potentials in accumbens evoked by stimulating prefrontal cortex was reduced for up to 6 hours after acute cocaine in daily cocaine withdrawn animals. These data indicate that daily cocaine pretreatment dysregulates dendritic spine plasticity elicited by a subsequent cocaine injection.
Keywords: cocaine, nucleus accumbens, actin, dendritic spine, postsynaptic density, fields