ArticleMetabolic brain disease2019
Re-examining the role of ventral tegmental area dopaminergic neurons in motor activity and reinforcement by chemogenetic and optogenetic manipulation in mice.
Article in Metabolic brain disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- Neural circuits regulating activity-based anorexia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration.eLife · 2025Article
- α2-Adrenergic Receptors in Hypothalamic Dopaminergic Neurons: Impact on Food Intake and Energy Expenditure.International journal of molecular sciences · 2025Article
- A Novel Method for the Locomotion Control of a Rat Robot via the Electrical Stimulation of the Ventral Tegmental Area and Nigrostriatal Pathway.Brain sciences · 2025Article
- Tyrosine Hydroxylase-Positive Nucleus Accumbens Neurons Influence Delay Discounting in a Mouse T-Maze Task.eNeuro · 2024Article
- Optical Intracranial Self-Stimulation (oICSS): A New Behavioral Model for Studying Drug Reward and Aversion in Rodents.International journal of molecular sciences · 2024Review
- Comparison of three DREADD agonists acting on Gq-DREADDs in the ventral tegmental area to alter locomotor activity in tyrosine hydroxylase:Cre male and female rats.Behavioural brain research · 2023Article
- Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression.Molecular psychiatry · 2023Article
- A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum.Neural regeneration research · 2023Article
- Astrocytes mediate long-lasting synaptic regulation of ventral tegmental area dopamine neurons.Nature neuroscience · 2022Article
- Illuminating subcortical GABAergic and glutamatergic circuits for reward and aversion.Neuropharmacology · 2021Review
- Optogenetic brain-stimulation reward: A new procedure to re-evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter-Cre mice.Addiction biology · 2021Article
- Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease.Biomedicines · 2021Review
- Impact of Acute and Persistent Excitation of Prelimbic Pyramidal Neurons on Motor Activity and Trace Fear Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit.Frontiers in cellular neuroscience · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The precise contributions of ventral tegmental area (VTA) dopaminergic (DAergic) neurons to reward-related behaviors are a longstanding hot topic of debate. Whether the activity of VTA DAergic neurons directly modulates rewarding behaviors remains uncertain. In the present study, we investigated the fundamental role of VTA DAergic neurons in reward-related movement and reinforcement by employing dopamine transporter (DAT)-Cre transgenic mice expressing hM3Dq, hM4Di or channelrhodopsin 2 (ChR2) in VTA DAergic neurons through Cre-inducible adeno-associated viral vector transfection. On the one hand, locomotion was tested in an open field to examine motor activity when VTA DAergic neurons were stimulated or inhibited by injection of the hM3Dq or hM4Di ligand clozapine-N-oxide (CNO), respectively. CNO injection to selectively activate or inhibit VTA DAergic neurons significantly increased or decreased locomotor activity, respectively, compared with vehicle injection, indicating that VTA DAergic neuron stimulation is directly involved in the regulation of motor activity. On the other hand, we used the optical intracranial self-stimulation (oICSS) model to investigate the causal link between reinforcement and VTA DAergic neurons. Active poking behavior but not inactive poking behavior was significantly escalated in a frequency- and pulse duration-dependent manner. In addition, microdialysis revealed that the concentration of dopamine (DA) in the nucleus accumbens (NAc) was enhanced by selective optogenetic activation of VTA DAergic neurons. Furthermore, systemic administration of a DA D1 receptor antagonist significantly decreased oICSS reinforcement. Our research profoundly demonstrates a direct regulatory role of VTA DAergic neurons in movement and reinforcement and provides meaningful guidance for the development of novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.
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