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

Abstract

Many reports show that repeated cocaine administration increases dendritic spine density in medium spiny neurons of the nucleus accumbens, but there is less agreement regarding the persistence of these changes. In this review we examine these discrepancies by systematically categorizing papers that measured cocaine-induced changes in accumbal spine density. We compare published reports based on withdrawal time, short versus long duration of cocaine administration, environmental pairing with cocaine, and core/shell subregion specificity. Together, these studies suggest that cocaine exposure induces rapid and dose-dependent increases in spine density in accumbens neurons that may play a role in the maintenance of cocaine use and vulnerability to early relapse, but are not a factor in behavioral changes associated with longer abstinence.

Figure 1. Time course of cocaine-induced increases in spine density in nucleus accumbens

The percentage of studies reporting cocaine-induced spine changes over withdrawal gradually decreases from 100% at early time points (<1 day) to ~ 50% after 1 month. No studies report changes after 3 months of withdrawal. A table reporting the number of positive versus negative reports is given below.

Figure 2. Short- and long-term cocaine administration periods differentially affect the persistence of cocaine-induced spine density increases in nucleus accumbens

Reports of cocaine-induced spine density changes were grouped into short-term (3–11 days, green) and long-term (12–37 days, blue) days of cocaine treatment. A dashed blue line indicates no long-term dosing study examined time points at <24 hours of cocaine withdrawal. A table reporting the number of positive versus negative reports is given below.

Figure 3. Evidence that cocaine-induced changes in spine density in nucleus accumbens is independent of environmental context

Reports of cocaine-induced spine density changes were grouped based on home cage cocaine treatments or treatments in a distinct cocaine-paired environment. There is no relationship between the cocaine treatment environment and the longevity of spine density increases in published reports. A table reporting the number of positive versus negative reports is given below.

Figure 4. Cocaine-induced spine density changes are found more often in the accumbens shell

Changes in the shell (blue line) were reported more often than changes in the core (black line) at all time points, including <24hrs. A table reporting the number of positive versus negative reports is given below.