Transfer of Neuroplasticity from Nucleus Accumbens Core to Shell Is Required for Cocaine Reward

Abstract

It is well established that cocaine induces an increase of dendritic spines density in some brain regions. However, few studies have addressed the role of this neuroplastic changes in cocaine rewarding effects and have often led to contradictory results. So, we hypothesized that using a rigorous time- and subject-matched protocol would demonstrate the role of this spine increase in cocaine reward. We designed our experiments such as the same animals (rats) were used for spine analysis and behavioral studies. Cocaine rewarding effects were assessed with the conditioned place preference paradigm. Spines densities were measured in the two subdivisions of the nucleus accumbens (NAcc), core and shell. We showed a correlation between the increase of spine density in NAcc core and shell and cocaine rewarding effects. Interestingly, when cocaine was administered in home cages, spine density was increase in NAcc core only. With anisomycin, a protein synthesis inhibitor, injected in the core we blocked spine increase in core and shell and also cocaine rewarding effects. Strikingly, whereas injection of this inhibitor in the shell immediately after conditioning had no effect on neuroplasticity or behavior, its injection 4 hours after conditioning was able to block neuroplasticity in shell only and cocaine-induced place preference. Thus, it clearly appears that the neuronal plasticity in the NAcc core is essential to induce plasticity in the shell, necessary for cocaine reward. Altogether, our data revealed a new mechanism in the NAcc functioning where a neuroplasticity transfer occurred from core to shell.

Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5 signaling in the nucleus accumbens

“…Considering that these are not observed following repeated infusions of amphetamine into the VTA, it is likely that they reflect associative drug conditioning rather than nonassociative sensitization (Singer et al , 2009). Consistent with this possibility, Marie et al (2012) showed that the development of cocaine CPP correlates with increased dendritic spine density in the NAcc. Thus, preventing these increases in NAcc dendritic spine density normally observed in rats exposed to systemic amphetamine would be predicted to inhibit the development of conditioning while preserving the induction of sensitization.…”

Fragile X Mental Retardation Protein Regulates Synaptic and Behavioral Plasticity to Repeated Cocaine Administration

“…Similar to our current findings, a recent report suggests that the dendritic spine density increase is not required for behavioral sensitization, but does underlie incentive sensitization (Wang et al, 2013), a process whereby cocaine experience increases later sensitivity to cocaine reward. A relationship between cocaine-induced alterations in NAc spine density and CPP has also been proposed (Dietz et al, 2012; Marie et al, 2012; Maze et al, 2010; Russo et al, 2009). While we did not specifically look at dendritic spine density changes in WT or Fmr1 KO mice under cocaine CPP conditions ( e.g., 7.5 mg/kg cocaine × 2 injections), we suspect that changes in WT mice would not be observed under these low dose conditions; however, in the future, it will be important to test this idea more directly.…”

It's only a matter of time: longevity of cocaine-induced changes in dendritic spine density in the nucleus accumbens

“…Most papers agree that spine increases can be found at early cocaine withdrawal times from 1 to 10 days [5,6,16–27]. One noteworthy exception is from Smith et al who observed no changes in wild-type control mice, but did find changes in Fragile × Mental Retardation Protein knockout mice [28].…”

“…As shown in Figure 2, all papers with shorter cocaine treatment regimens report significant increases in spines after < 24 hours withdrawal [5,7,8,10–15]. From 1–10 days after withdrawal from cocaine, most of these short treatment studies report that cocaine-induced dendritic spines are still evident in nucleus accumbens MSNs [5,16–18], but Smith et al found no changes [28]. Increased spines are observed from 11–20 days of withdrawal in at least three reports using short duration cocaine treatments [29–31], but three other studies found no increases in spine density in this time frame [34–36].…”