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Available alternative incentives modulate anticipatory nucleus accumbens activation.

ABSTRACT: A reward or punishment can seem better or worse depending on what else might have happened. Little is known, however, about how neural representations of an anticipated incentive might be influenced by the available alternatives. We used event-related FMRI to investigate the activation in the nucleus accumbens (NAcc), while we varied the available alternative incentives in a monetary incentive delay task. Some task blocks included only uncertain gains and losses; others included the same uncertain gains and losses intermixed with certain gains and losses. The availability of certain gains and losses increased NAcc activation for uncertain losses and decreased the difference between uncertain gains and losses. We suggest that this pattern of activation can result from reference point changes across blocks, and that the worst available loss may serve as an important anchor for NAcc activation. These findings imply that NAcc activation represents anticipated incentive value relative to the current context of available alternative gains and losses.

SUBMITTER: Cooper JC

PROVIDER: S-EPMC2799954 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Available alternative incentives modulate anticipatory nucleus accumbens activation.

Cooper Jeffrey C JC Hollon Nick G NG Wimmer G Elliott GE Knutson Brian B

Social cognitive and affective neuroscience 20091020 4

A reward or punishment can seem better or worse depending on what else might have happened. Little is known, however, about how neural representations of an anticipated incentive might be influenced by the available alternatives. We used event-related FMRI to investigate the activation in the nucleus accumbens (NAcc), while we varied the available alternative incentives in a monetary incentive delay task. Some task blocks included only uncertain gains and losses; others included the same uncerta ...[more]

PMID: 19843618

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Project description:Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior.

Dataset Information

Available alternative incentives modulate anticipatory nucleus accumbens activation.

Publications

Available alternative incentives modulate anticipatory nucleus accumbens activation.

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