ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2019
Dorsal raphe serotonin neurons inhibit operant responding for reward via inputs to the ventral tegmental area but not the nucleus accumbens: evidence from studies combining optogenetic stimulation and serotonin reuptake inhibition.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
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- Behavioral impact of chemogenetic manipulations of 5-HT DRN neurons in transgenic Tph2-iCre rats.Psychopharmacology · 2026Article
- Dopamine and serotonin neurotransmissions exert complementary control over primate approach and avoidance.Translational psychiatry · 2025Article
- Optogenetic Stimulation of Novel Tph2-Cre Rats Advances Insight into Serotonin's Role in Locomotion, Reinforcement, and Compulsivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Exploring the effects of adolescent social isolation stress on the serotonin system and ethanol-motivated behaviors.Psychopharmacology · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- Treatment-resistant depression: molecular mechanisms and management.Molecular biomedicine · 2024Review
- The nucleus accumbens in reward and aversion processing: insights and implications.Frontiers in behavioral neuroscience · 2024Review
- GABAergic miR-34a regulates Dorsal Raphè inhibitory transmission in response to aversive, but not rewarding, stimuli.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges.Frontiers in pharmacology · 2023Review
- The long noncoding RNA FEDORA is a cell type- and sex-specific regulator of depression.Science advances · 2022Article
- Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice.Molecular psychiatry · 2022Article
- A serotonin-deficient rat model of neurogenic hypertension: influence of sex and sympathetic vascular tone.Journal of neurophysiology · 2022Article
- Optogenetic Stimulation of Midbrain Dopamine Neurons Produces Striatal Serotonin Release.ACS chemical neuroscience · 2022Article
- PtNPs/Short MWCNT-PEDOT: PSS-Modified Microelectrode Array to Detect Neuronal Firing Patterns in the Dorsal Raphe Nucleus and Hippocampus of Insomnia Rats.Micromachines · 2022Article
- The Combination of Galanin (1-15) and Escitalopram in Rats Suggests a New Strategy for Alcohol Use Disorder Comorbidity with Depression.Biomedicines · 2022Article
- Aversive motivation and cognitive control.Neuroscience and biobehavioral reviews · 2022Review
- Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms.Frontiers in psychiatry · 2022Review
- Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System.International journal of molecular sciences · 2021Review
- Serotonergic regulation of the dopaminergic system: Implications for reward-related functions.Neuroscience and biobehavioral reviews · 2021Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The monoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts an inhibitory influence over motivation, but the circuits mediating this are unknown. Here, we used an optogenetic approach to isolate the contribution of dorsal raphe nucleus (DRN) 5-HT neurons and 5-HT innervation of the mesolimbic dopamine (DA) system to motivated behavior in mice. We found that optogenetic stimulation of DRN 5-HT neurons enhanced downstream 5-HT release, but this was not sufficient to inhibit operant responding for saccharin, a measure of motivated behavior. However, combining optogenetic stimulation of DRN 5-HT neurons with a low dose of the selective serotonin reuptake inhibitor (SSRI) citalopram synergistically reduced operant responding. We then examined whether these effects could be recapitulated if optogenetic stimulation specifically targeted 5-HT terminals in the ventral tegmental area (VTA) or nucleus accumbens (NAc) of the mesolimbic DA system. Optogenetic stimulation of 5-HT input to the VTA combined with citalopram treatment produced a synergistic decrease in responding for saccharin, resembling the changes produced by targeting 5-HT neurons in the DRN. However, this effect was not observed when optogenetic stimulation targeted 5-HT terminals in the NAc. Taken together, these results suggest that DRN 5-HT neurons exert an inhibitory influence over operant responding for reward through a direct interaction with the mesolimbic DA system at the level of the VTA. These studies support an oppositional interaction between 5-HT and DA systems in controlling motivation and goal-directed behavior, and have important implications for the development and refinement of treatment strategies for psychiatric disorders such as depression and addiction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.