ArticleProceedings of the National Academy of Sciences of the United States of America2016
Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Paradoxical Ventral Tegmental Area GABA Signaling Drives Enhanced Morphine Reward After Adolescent Nicotine.Biological psychiatry · 2026Article
- Medial prefrontal cortical neurotransmitters reactive to relapse-promoting and relapse-suppressing cues in male rats trained to self-administer cocaine or alcohol.Addiction neuroscience · 2026Article
- Article
- Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.Science advances · 2025Article
- ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.Nature communications · 2024Article
- Receptor and metabolic insights on the ability of caffeine to prevent alcohol-induced stimulation of mesolimbic dopamine transmission.Translational psychiatry · 2024Article
- Receptor and metabolic insights on the ability of caffeine to prevent alcohol-induced stimulation of mesolimbic dopamine transmission.Research square · 2024Article
- Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction.Nature communications · 2023Article
- Differential roles of diacylglycerol lipase (DAGL) enzymes in nicotine withdrawal.Brain research · 2023Article
- Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence.International journal of molecular sciences · 2021Review
- Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models.The Journal of clinical investigation · 2021Article
- A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Endocannabinoid-Like Lipid Neuromodulators in the Regulation of Dopamine Signaling: Relevance for Drug Addiction.Frontiers in synaptic neuroscience · 2020Review
- Druggable Targets in Endocannabinoid Signaling.Advances in experimental medicine and biology · 2020Review
- Nicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement.The European journal of neuroscience · 2019Review
- Amino acid modulation of dopamine in the nucleus accumbens mediates sex differences in nicotine withdrawal.Addiction biology · 2018Article
- GABA Uptake Inhibition Reduces In Vivo Extraction Fraction in the Ventral Tegmental Area of Long Evans Rats Measured by Quantitative Microdialysis Under Transient Conditions.Neurochemical research · 2018Article
- Constitutive Increases in Amygdalar Corticotropin-Releasing Factor and Fatty Acid Amide Hydrolase Drive an Anxious Phenotype.Biological psychiatry · 2017Article
- Endocannabinoid modulation of dopamine neurotransmission.Neuropharmacology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE.
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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.