ArticleeNeuro
Locomotor- and Reward-Enhancing Effects of Cocaine Are Differentially Regulated by Chemogenetic Stimulation of Gi-Signaling in Dopaminergic Neurons.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 62 citations in OpenAlex.
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- Submedius thalamic inputs shape the presynaptic architecture of layer 5 orbitofrontal cortex in mice.iScience · 2026Article
- TMEM16A ablation in cholinergic medial habenula neurons induces early-onset schizophrenia-like phenotypes in mice.Molecular brain · 2026Article
- Cocaine remodels mFrontiers in cellular neuroscience · 2026Article
- Integrating optical neuroscience tools into touchscreen operant systems.Nature protocols · 2025Review
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.Psychopharmacology · 2025Article
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.bioRxiv : the preprint server for biology · 2024Article
- Role of Dopamine Neurons in Familiarity.bioRxiv : the preprint server for biology · 2023Article
- 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
- Behavioral encoding across timescales by region-specific dopamine dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Review
- Divergent brainstem opioidergic pathways that coordinate breathing with pain and emotions.Neuron · 2022Article
- Chemogenetic inhibition of trigeminal ganglion neurons attenuates behavioural and neural pain responses in a model of trigeminal neuropathic pain.European journal of pain (London, England) · 2022Article
- VTA MC3R neurons control feeding in an activity- and sex-dependent manner in mice.Neuropharmacology · 2021Article
- 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
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Dopamine plays a key role in the cellular and behavioral responses to drugs of abuse, but the implication of metabotropic regulatory input to dopaminergic neurons on acute drug effects and subsequent drug-related behavior remains unclear. Here, we used chemogenetics [Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)] to modulate dopamine signaling and activity before cocaine administration in mice. We show that chemogenetic inhibition of dopaminergic ventral tegmental area (VTA) neurons differentially affects locomotor and reward-related behavioral responses to cocaine. Stimulation of Gi-coupled DREADD (hM4Di) expressed in dopaminergic VTA neurons persistently reduced the locomotor response to repeated cocaine injections. An attenuated locomotor response was seen even when a dual-viral vector approach was used to restrict hM4Di expression to dopaminergic VTA neurons projecting to the nucleus accumbens. Surprisingly, despite the attenuated locomotor response, hM4Di-mediated inhibition of dopaminergic VTA neurons did not prevent cocaine sensitization, and the inhibitory effect of hM4Di-mediated inhibition was eliminated after withdrawal. In the conditioned place-preference paradigm, hM4Di-mediated inhibition did not affect cocaine-induced place preference; however, the extinction period was extended. Also, hM4Di-mediated inhibition had no effect on preference for a sugar-based reward over water but impaired motivation to work for the same reward in a touchscreen-based motivational assay. In addition, to support that VTA dopaminergic neurons operate as regulators of reward motivation toward both sugar and cocaine, our data suggest that repeated cocaine exposure leads to adaptations in the VTA that surmount the ability of Gi-signaling to suppress and regulate VTA dopaminergic neuronal activity.
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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.