ArticleMolecular psychiatry2020
Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 160 papers, 3 of them syntheses that pooled it.
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Who cites it
160 citing papers in PubMed, 3 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- Pooled it
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- Response Flexibility: The Role of the Lateral Habenula.Frontiers in behavioral neuroscience · 2022Pooled it
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- Strain-Dependent Network Activity Differences Underlie Social Decision-Making in Male Mice.eNeuro · 2026Article
- Striatal control of amygdalar acetylcholine release during salience-associated processing.Nature neuroscience · 2026Article
- The Endogenous Opioid System in Compulsive Eating.Brain sciences · 2026Review
- Dual regulatory roles of CPT1C in chronic stress-induced depression-related outcomes.Molecular psychiatry · 2026Article
- Volitional cocaine taking engages distinct medium spiny neuron and astrocyte transcriptional programs in the rat nucleus accumbens.bioRxiv : the preprint server for biology · 2026Article
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- Nucleus accumbens medial shell D1 and D2 medium spiny neurons signal the valence of conditioned stimuli in a sex-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The oxytocin system mediates behavioral and neurobiological alterations associated with early adversity.Molecular psychiatry · 2026Article
- Music engages the phasic dopaminergic D1-receptor system in humans: a PET-fMRI study using [European journal of nuclear medicine and molecular imaging · 2026Article
- Temporal cortex astrocytic Gi-GPCR signaling regulates learned threat responses.bioRxiv : the preprint server for biology · 2026Article
- D3 dopamine receptors implicate a striatal neuronal subtype in the aversive effects of the antipsychotic drug quetiapine.bioRxiv : the preprint server for biology · 2026Article
- MeCP2 regulates cell-type-specific functions of depressive-like symptoms in the nucleus accumbens.Experimental & molecular medicine · 2026Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deficits in decoding rewarding (and aversive) signals are present in several neuropsychiatric conditions such as depression and addiction, emphasising the importance of studying the underlying neural circuits in detail. One of the key regions of the reward circuit is the nucleus accumbens (NAc). The classical view on the field postulates that NAc dopamine receptor D1-expressing medium spiny neurons (D1-MSNs) convey reward signals, while dopamine receptor D2-expressing MSNs (D2-MSNs) encode aversion. Here, we show that both MSN subpopulations can drive reward and aversion, depending on their neuronal stimulation pattern. Brief D1- or D2-MSN optogenetic stimulation elicited positive reinforcement and enhanced cocaine conditioning. Conversely, prolonged activation induced aversion, and in the case of D2-MSNs, decreased cocaine conditioning. Brief stimulation was associated with increased ventral tegmenta area (VTA) dopaminergic tone either directly (for D1-MSNs) or indirectly via ventral pallidum (VP) (for D1- and D2-MSNs). Importantly, prolonged stimulation of either MSN subpopulation induced remarkably distinct electrophysiological effects in these target regions. We further show that blocking κ-opioid receptors in the VTA (but not in VP) abolishes the behavioral effects induced by D1-MSN prolonged stimulation. In turn, blocking δ-opioid receptors in the VP (but not in VTA) blocks the behavioral effects elicited by D2-MSN prolonged stimulation. Our findings demonstrate that D1- and D2-MSNs can bidirectionally control reward and aversion, explaining the existence of controversial studies in the field, and highlights that the proposed striatal functional opposition needs to be reconsidered.
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