ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Inhibition of endocannabinoid degradation rectifies motivational and dopaminergic deficits in the Q175 mouse model of Huntington's disease.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Endocannabinoid metabolism at VTA GABAergic neurons gates motivation for social, but not food, reward.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Perinatal exposure to delta-9-tetrahydrocannabinol (THC) alters goal-directed behavior and dopamine functioning in wistar rats.Psychopharmacology · 2026Article
- ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.Nature communications · 2024Article
- A helping HAND: therapeutic potential of MAGL inhibition against HIV-1-associated neuroinflammation.Frontiers in immunology · 2024Article
- Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction.Nature communications · 2023Article
- Article
- Regulation of glutamate homeostasis in the nucleus accumbens by astrocytic CB1 receptors and its role in cocaine-motivated behaviors.Addiction neuroscience · 2022Article
- Striatal Indirect Pathway Dysfunction Underlies Motor Deficits in a Mouse Model of Paroxysmal Dyskinesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Targeting Monoacylglycerol Lipase in Pursuit of Therapies for Neurological and Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2021Review
- Chronic Augmentation of Endocannabinoid Levels Persistently Increases Dopaminergic Encoding of Reward Cost and Motivation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cocaine-induced increases in motivation require 2-arachidonoylglycerol mobilization and CB1 receptor activation in the ventral tegmental area.Neuropharmacology · 2021Article
- Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release.Frontiers in synaptic neuroscience · 2021Review
- Age-Dependent Degradation of Locomotion Encoding in Huntington's Disease R6/2 Model Mice.Journal of Huntington's disease · 2021Article
- A Guide to Targeting the Endocannabinoid System in Drug Design.International journal of molecular sciences · 2020Review
- Cortical and Striatal Circuits in Huntington's Disease.Frontiers in neuroscience · 2020Review
- Reduced nucleus accumbens enkephalins underlie vulnerability to social defeat stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Accumbal Dopamine Release Tracks the Expectation of Dopamine Neuron-Mediated Reinforcement.Cell reports · 2019Article
- A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice.Frontiers in neurology · 2019Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Prominent motor deficits (e.g., chorea) that typify Huntington's disease (HD) arise following a prolonged prodromal stage characterized by psychiatric disturbances. Apathy, a disorder of motivation characterized by diminished goal-directed behavior, is one of the earliest and most common psychiatric symptoms in HD, but the underlying neurobiology is unclear and treatment options are limited. Alterations in the endocannabinoid (eCB) and dopamine systems represent prominent pathophysiological markers in HD that-similar to motivational deficits-present early and decline across disease progression. Whether changes in dopamine and eCB systems are associated with specific behavioral impairments in HD and whether these deficits are amenable to viable treatments is unknown. Here, we show that dopaminergic encoding of effortful drive progressively declines with age in an HD mouse model, and is restored by elevating tissue levels of the eCB 2-arachidonoylglycerol (2-AG) through targeted inhibition of its enzymatic degradation. This work supports aberrant dopaminergic encoding of reward as a neurobiological correlate of apathy in HD, and indicates that cannabinoid receptor-based therapies may benefit neuropsychiatric care for HD.
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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.