ArticleBiological psychiatry2018
Increased Alcohol Seeking in Mice Lacking Gpr88 Involves Dysfunctional Mesocorticolimbic Networks.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Age-dependent transcriptomic effects of morphine in the frontal cortex of female mice.Neuropharmacology · 2026Article
- GPR88 localization to primary cilia in neurons is cell-type specific.Life science alliance · 2026Article
- Robust automated preclinical fMRI preprocessing via a multi-stage dilated convolutional Swin Transformer affine registration.Frontiers in neuroscience · 2025Article
- The GPR88 Agonist RTI-122 Reduces Alcohol-Related Motivation and Consumption.Addiction biology · 2025Article
- Effects of adolescent alcohol exposure on oligodendrocyte lineage cells and myelination in mice: Age and subregion differences.IBRO neuroscience reports · 2024Article
- Identification and validation of a novel geneiScience · 2024Article
- Differential regulation of G protein-coupled receptor-associated proteins in the caudate and the putamen of cynomolgus macaques following chronic ethanol drinking.Journal of neurochemistry · 2024Article
- Orphan peptide and G protein-coupled receptor signalling in alcohol use disorder.British journal of pharmacology · 2024Review
- Manipulating ΔFOSB in D1-Type Medium Spiny Neurons of the Nucleus Accumbens Reshapes Whole-Brain Functional Connectivity.Biological psychiatry · 2024Article
- Cilia loss on distinct neuron populations differentially alters cocaine-induced locomotion and reward.Journal of psychopharmacology (Oxford, England) · 2024Article
- Design, Synthesis, and Structure-Activity Relationship Studies of Novel GPR88 Agonists (4-Substituted-phenyl)acetamides Based on the Reversed Amide Scaffold.ACS chemical neuroscience · 2024Article
- Article
- Reduced dopamine release in Dcc haploinsufficiency male mice abolishes the rewarding effects of cocaine but not those of morphine and ethanol.Psychopharmacology · 2023Article
- Improvement of the Metabolic Stability of GPR88 Agonist RTI-13951-33: Design, Synthesis, and Biological Evaluation.Journal of medicinal chemistry · 2023Article
- Synthesis and pharmacological validation of a novel radioligand for the orphan GPR88 receptor.Bioorganic & medicinal chemistry letters · 2023Article
- The GPR88 agonist RTI-13951-33 reduces alcohol drinking and seeking in mice.Addiction biology · 2022Article
- The orphan receptor GPR88 controls impulsivity and is a risk factor for Attention-Deficit/Hyperactivity Disorder.Molecular psychiatry · 2022Article
- Bmal1 in the striatum influences alcohol intake in a sexually dimorphic manner.Communications biology · 2021Article
- Chronic generalized pain disrupts whole brain functional connectivity in mice.Brain imaging and behavior · 2021Article
Corrections and comments
- Erratum issuedErratum.2018
Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
Abstract
backgoundAlcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively sought for prevention and treatment. The orphan G protein-coupled receptor GPR88 is enriched in mesocorticolimbic pathways, and Gpr88 knockout mice show hyperactivity and risk-taking behavior, but a potential role for this receptor in drug abuse has not been examined.
methodsWe tested Gpr88 knockout mice for alcohol-drinking and -seeking behaviors. To gain system-level understanding of their alcohol endophenotype, we also analyzed whole-brain functional connectivity in naïve mice using resting-state functional magnetic resonance imaging.
resultsGpr88 knockout mice showed increased voluntary alcohol drinking at both moderate and excessive levels, with intact alcohol sedation and metabolism. Mutant mice also showed increased operant responding and motivation for alcohol, while food and chocolate operant self-administration were unchanged. Alcohol place conditioning and alcohol-induced dopamine release in the nucleus accumbens were decreased, suggesting reduced alcohol reward in mutant mice that may partly explain enhanced alcohol drinking. Seed-based voxelwise functional connectivity analysis revealed significant remodeling of mesocorticolimbic centers, whose hallmark was predominant weakening of prefrontal cortex, ventral tegmental area, and amygdala connectional patterns. Also, effective connectivity from the ventral tegmental area to the nucleus accumbens and amygdala was reduced.
conclusionsGpr88 deletion disrupts executive, reward, and emotional networks in a configuration that reduces alcohol reward and promotes alcohol seeking and drinking. The functional connectivity signature is reminiscent of alterations observed in individuals at risk for AUD. The Gpr88 gene, therefore, may represent a vulnerability/resilience factor for AUD, and a potential drug target for AUD treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.