The induction of behavioural sensitization is associated with cocaine‐induced structural plasticity in the core (but not shell) of the nucleus accumbens

Abstract

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi-Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.

Reduced Dopamine Terminal Function and Insensitivity to Cocaine Following Cocaine Binge Self-Administration and Deprivation

“…Cocaine and amphetamine appear to preferentially increase glucose utilization in the shell compared with the core of the Nac, and morphine, nicotine, cocaine, and amphetamine preferentially increased extracellular DA in the shell over the core (Pontieri et al, 1995(Pontieri et al, , 1996. In contrast, a number of papers suggest a preferential involvement of the NAc core in morphological changes associated with sensitization (Li et al, 2004), acquisition of opiate SA (Alderson et al, 2001;Hutcheson et al, 2001), and with relapse to cocaine use (McFarland and Kalivas, 2001). It would appear that both regions of the NAc subserve different roles in the reinforcing effects of drugs of abuse.…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…In all studies to date, both non-contingent and contingent cocaine or amphetamine administration were found to increase spine density, as well as dendritic branching on medium spiny GABAergic neurons within both the shell and core subregions of the NAC [198][199][200][201][202][203][204][205][206][207]. Similarly, repeated treatment with both psychomotor stimulants increase spine density and branching of the apical, and to a lesser extent the basalar, dendrites of glutamatergic pyramidal neurons within the PFC [198][199][200][201]204,205].…”

The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration

“…This enhanced behavioral response peaks at time points that are well beyond the acute withdrawal phase and persists for months in abstinent rats (Vanderschuren and Kalivas 2000;Li et al, 2004;Giorgi et al, 2007). The repeated exposure to psychostimulants (either contingent or non-contingent) may also lead to the development of sensitization to their incentive-motivational effects (Horger et al, 1990;Piazza et al, 1990;Robinson and Berridge, 2003;Vanderschuren and Everitt, 2005;Morgan et al, 2006).…”

“…It has been proposed that these neural circuits encode and associate information about a primary reinforcer like cocaine with motivated behavior and/or environmental stimuli (Everitt and Wolf, 2002;Schultz, 2002;Hollander and Carelli, 2007). Adaptive changes in this neural circuitry are also believed to underlie the long-term increment in the locomotor activation of rodents (ie, behavioral sensitization) elicited by the repeated exposure to cocaine (Vanderschuren and Kalivas, 2000;Nestler, 2001;Li et al, 2004;Vezina, 2004). There is also experimental evidence that sensitization-like processes may account for the compulsive pattern of drug-seeking and the vulnerability to relapse that persists long after the cessation of psychostimulant use in humans (Robinson and Berridge, 2003).…”