Differential control over cocaine-seeking behavior by nucleus accumbens core and shell

Abstract

Nucleus accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of continuous reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

“…The finding of Di Ciano and Everitt are in agreement with those demonstrating that permanent NAc core lesions had a more pronounced effect than NAc shell lesions on responding reinforced by heroin or cocaine cues in this procedure (Hutcheson et al, 2001;Ito et al, 2004). Fuchs et al (2004) reported that reversible inactivation (muscimol + baclofen injections) of the NAc core, but not the shell, attenuates discrete cue-induced reinstatement of cocaine seeking; the discrete cues were presented contingently during testing.…”

“…This anatomical distinction is important because there are reports that NAc core and shell differentially modulate the conditioned and unconditioned behavioral effects of opiate and psychostimulant drugs (Everitt and Wolf, 2002;Di Chiara et al, 2004;Ikemoto and Wise, 2004). For example, reversible or permanent lesions of the NAc core, but not the shell, attenuate cue-controlled cocaine seeking, as measured by the second-order schedule and the cue-induced reinstatement procedures (Fuchs et al, 2004;Ito et al, 2004); see also Di Ciano and Everitt (2001) and Hyytia and Backstrom (2005) for similar findings with ionotropic glutamate receptor antagonists. On the other hand, 6-OHDA lesions of the NAc shell, but not the core, attenuate the reinforcing effects of amphetamine, as measured in the conditioned place preference procedure (Sellings and Clarke, 2003).…”

Mice with Chronically Elevated Dopamine Exhibit Enhanced Motivation, but not Learning, for a Food Reward

“…Under the concurrent choice task, administration of dopamine antagonist in both the core and the shell was reported to induce a shift from lever pressing to consumption of the freely available food. Although the specific function of nucleus accumbens core vs shell is still a matter of debate , the shell may be important in the response to unconditioned reward and Pavlovian cues, whereas the core may be more important in selection and expression of responses as a function of the value of the reward (Corbit et al, 2001;Di Chiara et al, 2004;Everitt et al, 2001;Ito et al, 2004). In addition, food deprivation not only increases the locomotor activation induced by cocaine or amphetamine, but also induces a greater release of dopamine in the nucleus accumbens core, but not the shell (Cadoni et al, 2003;Carr, 2002).…”

Abstinence from Cocaine Self-Administration Heightens Neural Encoding of Goal-Directed Behaviors in the Accumbens

“…The nucleus accumbens (Acb) and associated regions are part of the 'brain reward system' and considered key neural substrates underlying addiction Le Moal, 1997, 2001;Ahmed and Koob, 2005;Everitt and Wolf, 2002;Ito et al, 2004;Wise, 1984). Recent studies have examined the effects of cocaine abstinence (withdrawal) on this system.…”