ArticleNeurobiology of disease2019
Knockout of latrophilin-3 in Sprague-Dawley rats causes hyperactivity, hyper-reactivity, under-response to amphetamine, and disrupted dopamine markers.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Altered striatal dopamine regulation in Adgrl3 knockout mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- The expanding roles of adhesion GPCRs in neural circuit assembly.Molecules and cells · 2026Review
- Loss of Thy1 in Cortico-Striatal Pathways Alters Response to Dopamine and Gabapentin.ASN neuro · 2026Article
- Memory processing in neurodevelopmental disorders: linking behavioral, circuits, and molecular scales.Frontiers in cellular neuroscience · 2026Review
- Animal models for the study of ADHD: the need for next-generation models.Frontiers in psychiatry · 2026Review
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Article
- Comparison of Sprague Dawley with Long Evans rats on a battery of widely used neurobehavioral tests.Physiology & behavior · 2025Article
- Effects of whole brain proton irradiation at conventional or ultra-high dose rate (FLASH), in adult male Sprague Dawley rats.Scientific reports · 2025Article
- Phasic dopamine release in two different rat models of attention-deficit/hyperactivity disorder: Spontaneously hypertensive rats (SHR) versus Lphn3 knockout rats.Neuroscience · 2025Article
- Review
- Genome-wide association study of delay discounting in Heterogeneous Stock rats.Genes, brain, and behavior · 2024Article
- Learning and Memory Impairments With Attention-Deficit/Hyperactivity Disorder.Physiological research · 2024Review
- The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models.Frontiers in psychiatry · 2024Review
- Genome-wide association study of delay discounting in Heterogenous Stock rats.bioRxiv : the preprint server for biology · 2023Article
- adgrl3.1-deficient zebrafish show noradrenaline-mediated externalizing behaviors, and altered expression of externalizing disorder-candidate genes, suggesting functional targets for treatment.Translational psychiatry · 2023Article
- Nucleus accumbens deep brain stimulation improves depressive-like behaviors through BDNF-mediated alterations in brain functional connectivity of dopaminergic pathway.Neurobiology of stress · 2023Article
- Novel non-stimulants rescue hyperactive phenotype in an adgrl3.1 mutant zebrafish model of ADHD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Attention deficit hyperactivity disorder is a pervasive developmental disorder characterized by inattention, impulsivity, and hyperactivity and is 75-90% heritable. Latrophilin-3 (LPHN3; or ADGRL(3)) is associated with a subtype of ADHD, but how it translates to symptoms is unknown. LPHN3 is a synaptic adhesion G protein coupled receptor that binds to fibronectin leucine rich transmembrane protein 3 and teneurin-3 (FLRT3 and TEN-3). We created a null mutation of Lphn3 (KO) in Sprague-Dawley rats using CRISPR/Cas9 to delete exon-3. The KO rats had no effects on reproduction or survival but reduced growth. KO females showed catch-up weight gain whereas KO males did not. We tested WT and KO littermates for home-cage activity, anxiety-like behavior, acoustic startle response, and activity after amphetamine challenge. Expression of Lphn3-related genes, monoamines, and receptors were determined. Lphn3 KO rats showed persistent hyperactivity, increased acoustic startle, reduced activity in response to amphetamine relative to baseline, and female-specific reduced anxiety-like behavior. Expression of Lphn1, Lphn2, and Flrt3 by qPCR and their protein products by western-blot analysis showed no compensatory upregulation. Striatal tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), and the dopamine transporter were increased and dopamine D1 receptor (DRD1) and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) decreased with no changes in DRD2, DRD4, vesicular monoamine transporter-2, N-methyl-d-aspartate (NMDA)-NR1, -NR2A, or -NR2B. LPHN3 is expressed in many brain regions but its function is largely unknown. Data from human, mouse, zebrafish, Drosophila and our new Lphn3 KO rat data collectively show that its disruption is significantly correlated with hyperactivity and associated striatal changes in dopamine markers.
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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.