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

doi:10.1016/j.neuroscience.2005.06.088

Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2005.06.088 Get 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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: (Available online 13 September 2005)

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Research paperBehaviourial neurosienceNucleus accumbens dopamine release is necessary and sufficient to promote the behavioral response to reward-predictive cues

Abstract

Section snippets

Animals

Results

Discussion

Conclusion

Acknowledgments

Passive exposure to a contextual discriminative stimulus reinstates cocaine-seeking behavior in rats

Pharmacol Biochem Behav

Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity

Behav Brain Res

Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments

Neuroscience

Neurobiology of motivationdouble dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent animals

Behav Neurosci

Stimuli associated with a single cocaine experience elicit long-lasting cocaine-seeking

Nat Neurosci

Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration

Eur J Neurosci

Conditioned changes in dopamine oxidation currents in the nucleus accumbens of rats by stimuli paired with self-administration or yoked-administration of d-amphetamine

Eur J Neurosci

Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of pavlovian approach behavior

J Neurosci

Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability

Behav Neurosci

Dissociation of Pavlovian and instrumental incentive learning under dopamine antagonists

Behav Neurosci

Discrete coding of reward probability and uncertainty by dopamine neurons

Science

Persistent cue-evoked activity of accumbens neurons after prolonged abstinence from self-administered cocaine

J Neurosci

Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats

J Neurosci

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

Nat Neurosci

Dopamine and conditioned reinforcement. I. Differential effects of amphetamine microinjections into striatal subregions

Psychopharmacology (Berl)

Conditioned reinstatement of drug-seeking behavior with a discrete compound stimulus classically conditioned with intravenous cocaine

Behav Neurosci

Responses of monkey dopamine neurons during learning of behavioral reactions

J Neurophysiol

Neuronal correlates of goal-based motor selection in the prefrontal cortex

Science

Reinstatement of drug-seeking behavior produced by heroin-predictive environmental stimuli

Psychopharmacology (Berl)

From motivation to actiona review of dopaminergic regulation of limbic-nucleus accumbens-ventral pallidum-pedunculopontine nucleus circuitries involved in limbic-motor integration

From motivation to actionfunctional interface between the limbic system and the motor system

Prog Neurobiol

Neurobiological constraints on behavioral models of motivation

Annu Rev Psychol

Dopamine overflow in the nucleus accumbens during extinction and reinstatement of cocaine self-administration behavior

Neuropsychopharmacology

Contrast enhancementa physiological effect of striatal dopamine?

Cell Tissue Res

Cue-evoked firing of nucleus accumbens neurons encodes motivational significance during a discriminative stimulus task

J Neurophysiol

Single neuron responses in amygdala of alert monkey during complex sensory stimulation with affective significance

J Neurosci

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