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Cited by 114Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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Desire and dread from the nucleus accumbens: cortical glutamate and subcortical GABA differentially generate motivation and hedonic impact in the rat.

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Faure, Alexis, Richard, Jocelyn M., Berridge, Kent C.·2010·PLoS ONE
DOI 10.1371/journal.pone.0011223PMC PMC2887893
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Abstract

BACKGROUND: GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. METHODOLOGY/PRINCIPAL FINDINGS: Microinjections of a GABA(A) agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic "liking" or "disliking" by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste "liking" (at rostral sites) versus "disliking" (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation. CONCLUSIONS/SIGNIFICANCE: We conclude that the nucleus accumbens contains two functional affective keyboards for amino-acid signals: a motivation-generating keyboard and a hedonic-generating keyboard. Corticolimbic glutamate signals and subcortical GABA signals equivalently engage the motivation keyboard to generate desire and-or dread. Only subcortical GABA signals additionally engage the hedonic keyboard to amplify affective "liking" and "disliking" reactions. We thus suggest that top-down cortical glutamate signals powerfully regulate motivation components, but are relatively unable to penetrate core hedonic components of emotion. That may carry implications of limits to therapeutic regulation of pathological emotions.

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Figures

Figure 1 Glutamatergic and GABAergic NAc Circuits. Green; glutamatergic inputs from medial prefrontal cortex, orbitofrontal cortex, hippocampus, thalamus, and basolateral amygdala are shown entering the NAc, where they synapse on distal dendrites of medium spiny neurons in NAc. Red; GABAergic inputs from ventral pallidum and ventral tegmental area, as well as GABAergic interneurons and axon collaterals from other medium spiny neurons are shown synapsing onto proximal dendrites and soma of medium spiny neurons within NAc.
Figure 1 Glutamatergic and GABAergic NAc Circuits. Green; glutamatergic inputs from medial prefrontal cortex, orbitofrontal cortex, hippocampus, thalamus, and basolateral amygdala are shown entering the NAc, where they synapse on distal dendrites of medium spiny neurons in NAc. Red; GABAergic inputs from ventral pallidum and ventral tegmental area, as well as GABAergic interneurons and axon collaterals from other medium spiny neurons are shown synapsing onto proximal dendrites and soma of medium spiny neurons within NAc.CC BY · PubMed Central
Figure 2 Summary maps of appetitive versus defensive motivation produced by GABA-A agonism and AMPA antagonism. Fos plume maps of appetitive eating versus defensive treading behavior generated by muscimol GABA stimulation (left) or DNQX AMPA blockade (right). Sites were designated as producing primarily appetitive (green symbols), defensive (red symbols) or mixed (yellow symbols) motivated behavior following muscimol and DNQX microinjections. Purely appetitive behavior (criteria for including a site was a >400 sec increase in feeding behavior) was primarily stimulated in rostral shell by both DNQX and muscimol, whereas defensive behavior (criteria for including a site was a >15 sec increase in treading behavior over vehicle levels) was primarily stimulated in caudal shell by both DNQX and muscimol. Histograms bars show mean change from vehicle (error bars = SEM) for both feeding (top) and defensive treading (bottom) at all rostrocaudal levels.
Figure 2 Summary maps of appetitive versus defensive motivation produced by GABA-A agonism and AMPA antagonism. Fos plume maps of appetitive eating versus defensive treading behavior generated by muscimol GABA stimulation (left) or DNQX AMPA blockade (right). Sites were designated as producing primarily appetitive (green symbols), defensive (red symbols) or mixed (yellow symbols) motivated behavior following muscimol and DNQX microinjections. Purely appetitive behavior (criteria for including a site was a >400 sec increase in feeding behavior) was primarily stimulated in rostral shell by both DNQX and muscimol, whereas defensive behavior (criteria for including a site was a >15 sec increase in treading behavior over vehicle levels) was primarily stimulated in caudal shell by both DNQX and muscimol. Histograms bars show mean change from vehicle (error bars = SEM) for both feeding (top) and defensive treading (bottom) at all rostrocaudal levels.CC BY · PubMed Central
Figure 3 Summary maps of hedonic and aversive shifts produced by GABA-A agonism and AMPA antagonism. Fos plume maps of sites where muscimol GABA stimulation (left) or DNQX AMPA blockade (right) produced hedonic (red symbols) or aversive (purple symbols) in orofacial reactions to a sweet/bitter sucrose-quinine mixture at 15 minutes post-microinjection. Criteria for including a site as hedonic was an increase >10 in ‘liking’ reactions and a decrease or no change in ‘disliking’ reactions. Criteria for including a site as aversive was an increase >10 in ‘disliking’ reactions and/or a decrease >10 in ‘liking’ reactions. Hedonic enhancement was produced by muscimol only a moderately rostral area just below the genu of the corpus callosum. Aversive enhancement was produced by muscimol throughout rostral shell, and in an area rostral to the hedonic enhancement zone, possibly extending into rostral pole of NAc. DNQX produced mostly ambivalent effects (white; no change, or simultaneously enhanced or suppressed ‘liking’ and ‘disliking’ reactions). Histograms bars show mean change from vehicle (error bars = SEM) for both hedonic ‘liking’ reactions (top) and aversive ‘disliking’ reactions (bottom) at all rostrocaudal levels.
Figure 3 Summary maps of hedonic and aversive shifts produced by GABA-A agonism and AMPA antagonism. Fos plume maps of sites where muscimol GABA stimulation (left) or DNQX AMPA blockade (right) produced hedonic (red symbols) or aversive (purple symbols) in orofacial reactions to a sweet/bitter sucrose-quinine mixture at 15 minutes post-microinjection. Criteria for including a site as hedonic was an increase >10 in ‘liking’ reactions and a decrease or no change in ‘disliking’ reactions. Criteria for including a site as aversive was an increase >10 in ‘disliking’ reactions and/or a decrease >10 in ‘liking’ reactions. Hedonic enhancement was produced by muscimol only a moderately rostral area just below the genu of the corpus callosum. Aversive enhancement was produced by muscimol throughout rostral shell, and in an area rostral to the hedonic enhancement zone, possibly extending into rostral pole of NAc. DNQX produced mostly ambivalent effects (white; no change, or simultaneously enhanced or suppressed ‘liking’ and ‘disliking’ reactions). Histograms bars show mean change from vehicle (error bars = SEM) for both hedonic ‘liking’ reactions (top) and aversive ‘disliking’ reactions (bottom) at all rostrocaudal levels.CC BY · PubMed Central
Figure 4 Fos plume examples for muscimol and DNQX. Colored plume maps for both muscimol (left) and DNQX (right) show local elevations or suppressions of Fos caused relative to vehicle (top). Muscimol produces an inhibitory “anti-plume” or an area of suppressed Fos expression (to 75% and 50% of vehicle levels), surrounding a small excitatory center of 200% vehicle levels. DNQX produces a larger, excitatory plume with areas of 200–400% vehicle level Fos expression. Examples of Fos expression produced by both vehicles (saline and the 50% saline/50% DMSO mixture) as well as muscimol and DNQX are shown on the bottom.
Figure 4 Fos plume examples for muscimol and DNQX. Colored plume maps for both muscimol (left) and DNQX (right) show local elevations or suppressions of Fos caused relative to vehicle (top). Muscimol produces an inhibitory “anti-plume” or an area of suppressed Fos expression (to 75% and 50% of vehicle levels), surrounding a small excitatory center of 200% vehicle levels. DNQX produces a larger, excitatory plume with areas of 200–400% vehicle level Fos expression. Examples of Fos expression produced by both vehicles (saline and the 50% saline/50% DMSO mixture) as well as muscimol and DNQX are shown on the bottom.CC BY · PubMed Central
Figure 5 Muscimol induced changes in hedonic and aversive reactions. Fos plume maps of sites where muscimol GABA-A stimulation produced changes in hedonic ‘liking’ reactions (A) or aversive ‘disliking’ reactions (B) to sucrose-quinine taste at 15 (left) and 60 minutes (right) post-microinjection. Muscimol primarily enhanced ‘liking’ reactions in a small moderately rostral area, beneath the genu of the corpus callosum. Muscimol microinjection at sites outside of this area tended to reduce hedonic ‘liking’ reactions and enhanced aversive ‘disliking’ reactions, especially in caudal regions of NAc medial shell. Histograms bars show mean change from vehicle (error bars = SEM) for both each reaction pattern at rostrocaudal and dorsoventral levels throughout medial shell.
Figure 5 Muscimol induced changes in hedonic and aversive reactions. Fos plume maps of sites where muscimol GABA-A stimulation produced changes in hedonic ‘liking’ reactions (A) or aversive ‘disliking’ reactions (B) to sucrose-quinine taste at 15 (left) and 60 minutes (right) post-microinjection. Muscimol primarily enhanced ‘liking’ reactions in a small moderately rostral area, beneath the genu of the corpus callosum. Muscimol microinjection at sites outside of this area tended to reduce hedonic ‘liking’ reactions and enhanced aversive ‘disliking’ reactions, especially in caudal regions of NAc medial shell. Histograms bars show mean change from vehicle (error bars = SEM) for both each reaction pattern at rostrocaudal and dorsoventral levels throughout medial shell.CC BY · PubMed Central
Figure 6 DNQX induced changes in hedonic and aversive reactions. Fos plume maps of sites where DNQX AMPA blockade produced changes in hedonic ‘liking’ reactions (A) or aversive ‘disliking’ reactions (B) to sucrose-quinine taste at 15 (left) and 60 minutes (right) post-microinjection. DNQX had little to no effect on both hedonic ‘liking’ reactions and aversive ‘disliking’ reactions. While some subjects did show changes in ‘liking’ or ‘disliking’ (as indicated by the sporadically colored symbols), no general pattern emerged. Histograms bars show mean change from vehicle (error bars = SEM) for both each reaction pattern at rostrocaudal and dorsoventral levels as marked along the medial shell.
Figure 6 DNQX induced changes in hedonic and aversive reactions. Fos plume maps of sites where DNQX AMPA blockade produced changes in hedonic ‘liking’ reactions (A) or aversive ‘disliking’ reactions (B) to sucrose-quinine taste at 15 (left) and 60 minutes (right) post-microinjection. DNQX had little to no effect on both hedonic ‘liking’ reactions and aversive ‘disliking’ reactions. While some subjects did show changes in ‘liking’ or ‘disliking’ (as indicated by the sporadically colored symbols), no general pattern emerged. Histograms bars show mean change from vehicle (error bars = SEM) for both each reaction pattern at rostrocaudal and dorsoventral levels as marked along the medial shell.CC BY · PubMed Central
Figure 7 Muscimol and DNQX-induced feeding and defensive treading behavior. Fos plume maps of appetitive eating (A) and defensive treading (B) behavior generated by muscimol GABA stimulation (left) or DNQX AMPA blockade (right). Scatter plots above Fos plume maps indicate behavioral changes exhibited by individual subjects; lines indicate the slope of the correlation between behavioral change (from vehicle) and distance rostral to bregma in mm (*p<.05; **p<.01). Histograms bars below and to the sides of the maps show mean change from vehicle (error bars = SEM) for each behavior at rostrocaudal and dorsoventral levels as marked along the medial shell.
Figure 7 Muscimol and DNQX-induced feeding and defensive treading behavior. Fos plume maps of appetitive eating (A) and defensive treading (B) behavior generated by muscimol GABA stimulation (left) or DNQX AMPA blockade (right). Scatter plots above Fos plume maps indicate behavioral changes exhibited by individual subjects; lines indicate the slope of the correlation between behavioral change (from vehicle) and distance rostral to bregma in mm (*p<.05; **p<.01). Histograms bars below and to the sides of the maps show mean change from vehicle (error bars = SEM) for each behavior at rostrocaudal and dorsoventral levels as marked along the medial shell.CC BY · PubMed Central

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  1. H Moore, 2001, Interactions between prefrontal cortical, hippocampal, and amygdalar inputs in regulating the activity of nucleus accumbens neurons., Biological Psychiatry, 49, 34

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Metadata

Authors
Faure, A., Richard, J. M., & Berridge, K. C.
Affiliations
University of Michigan (US)
Corresponding author
Faure, Alexis
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-06-18
Volume
5
Issue
6
Pages
e11223
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0011223
PMC
PMC2887893
OpenAlex
W2084903850
Cited by
114
References
81
Citations by year
2026: 1 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 10 · 2019: 10 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 11 · 2014: 11 · 2013: 7 · 2012: 9
FWCI
3.75
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (MH-63649, R01MH063649)
  • National Institute on Drug Abuse (DA015188, R01DA015188)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
nucleus accumbens shell, GABAergic neurotransmission, glutamatergic signaling, motivation, desire, dread, appetitive motivation, muscimol, DNQX, rostrocaudal gradient, emotion regulation
MeSH terms
Animals, Fear, Feeding Behavior, gamma-Aminobutyric Acid, Motivation, Muscimol, Nucleus Accumbens, Quinoxalines, Glutamic Acid, Rats

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