Elsevier

Neuroscience

Volume 135, Issue 4, 2005, Pages 1025-1033
Neuroscience

Research paper
Behaviourial neurosience
Nucleus accumbens dopamine release is necessary and sufficient to promote the behavioral response to reward-predictive cues

https://doi.org/10.1016/j.neuroscience.2005.06.088Get rights and content

Abstract

The nucleus accumbens is part of the neural circuit that controls reward-seeking in response to reward-predictive cues. Dopamine release in the accumbens is essential for the normal functioning of this circuit. Previous studies have shown that injection of dopamine receptor antagonists into the accumbens severely impairs an animal’s ability to perform operant behaviors specified by predictive cues. Furthermore, excitations and inhibitions of accumbens neurons evoked by such cues are abolished by inactivation of the ventral tegmental area, the major dopaminergic input to the accumbens. These results indicate that dopamine is necessary to elicit neural activity in the accumbens that drives the behavioral response to cues. Here we show that accumbens dopamine release is causal to the rats’ reward-seeking behavioral response by demonstrating that dopamine in this structure is both necessary and sufficient to promote the appropriate behavioral response to reward-predictive cues.

Section snippets

Animals

Male Long-Evans rats (275g) were obtained from Harlan (Indianapolis, IN, UA) and maintained on a 12-h light/dark cycle; experiments were performed during the light phase. Upon receipt, animals were allowed at least 1 week of ad libitum food and water before being placed on a restricted diet. Except where indicated, this consisted of 13g of BioServ pellets (1g each) and 20ml of water each day. Training began after 1 week of restriction. All procedures were approved by the Ernest Gallo Clinic &

Results

During experimental sessions, both PS cues (15% of correct responses to the cue were rewarded) and DS cues (100% of correct responses to the cue were rewarded) were presented in random order (Fig. 1A). Whereas animals responded to nearly 100% of DS presentations, they responded to only about 50% of PS presentations. The PS response probability was clearly dependent on the occasional reinforcement of PS responses and was not due to stimulus generalization from the DS to the PS. Three

Discussion

In the PS-DS task, animals responded to nearly all DS presentations, but responded to only approximately 50% of PS presentations. This behavior is consistent with previous observations that animals “match” their responding to the probability that reward will result from a particular action (Staddon and Cerutti, 2003). In this case, animals overmatched, since the response probability (50%) was greater than the reward probability (15%). The substantial degree of overmatching is likely due to the

Conclusion

In summary, the dopamine reuptake blocker GBR12909 specifically increased cue response probability in a task where animals respond to about half of cue presentations. The dopamine D1 receptor antagonist SCH23390 reduced responding to such cues. These results support the hypothesis that dopamine release in the NAc is necessary and sufficient for responding to reward-predictive cues, and therefore that NAc dopamine release causes animals to respond to such cues.

Acknowledgments

This work was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco; by the Wheeler Center for the Neurobiology of Addiction; by the Ernest Gallo Clinic and Research Center and by NIDA grants to H.L.F. We thank G. Hjelmstad for helpful discussions and K. Wakabayashi for technical assistance.

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