lepr flox mice  (Jackson Laboratory)

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a, Schematic of the combined Xenium spatial transcriptomics and pSTAT3 immunofluorescence workflow used to quantify leptin signaling across hypothalamic cell types in chow-fed and diet-induced obese (DIO) mice. b , UMAP embedding of neurons (17 populations; n=6 mice total) across all spatially profiled sections, colored by transcriptionally defined Lepr cell clusters. c , Marker gene expression across Lepr neuron subtypes, highlighting canonical cell type markers. d , UMAP embedding showing pSTAT3-positive Lepr neurons (green). e, Numbers of pSTAT3-positive cells across Lepr neuron subtypes in chow-fed and HFD-fed mice (n=3 mice per group; 2–3 sections per mouse). DIO increased pSTAT3 positivity nearly 10-fold overall (4.45±0.65% vs. 0.47±0.2%, P <0.001; generalized linear mixed-effects model with binomial distribution, animal as random effect). This was driven predominantly by Lepr/Glp1r neurons, which showed a >20-fold increase (21.1±1.1% vs. 0.33±0.2%, P <1×10⁻¹⁰) and accounted for >60% of all pSTAT3-positive Lepr neurons in DIO. P -values adjusted by Benjamini-Hochberg. f , Representative distribution of the each population of Lepr neurons across a single coronal section, color-coded as in b, c. Right panels show representative Xenium and immunofluorescence images showing spatial colocalization of Lepr, Glp1r, Trh , and pSTAT3 in the boxed areas of the larger panel. g , DIO-induced transcriptional changes in Lepr/Glp1r neurons, including increased expression of canonical leptin target genes ( Socs3, Nlrc5, Sbno2, Atf3; red) and immediate-early genes (e.g., Junb, Vgf ), indicating robust and sustained leptin signaling.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Spatial Transcriptomics, Immunofluorescence, Marker, Gene Expression, Expressing

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , UMAP embedding of all cells from Xenium in situ sequencing annotated by seurat cluster numbers. Colors illustrate clusters. b , Representative images from Xenium in spatial context. Colors match clusters in panel a. Top image from Xenium slide 1 and bottom image from Xenium slide 2. c , UMAP embeddings of all cells from Xenium in situ sequencing annotated by animal (left panel) or by diet; 15 weeks HFD (DIO) and chow (right panel). d , UMAP embeddings of all cells from Xenium in situ sequencing colored by expression of Slc17a6 (glutamatergic neurons), Gad1 (GABAergic neurons), Rax (tanycytes) and Lepr . e , UMAP embedding of all neurons from Xenium in situ sequencing colored by seurat cluster (left panel), by Campbell et al. label transfer annotations (middle panel), and by Rupp et al. label transfer annotations (right panel).

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: In Situ, Sequencing, Expressing

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Experimental design for snRNA-seq profiling of hypothalamic neurons across metabolic states: chow-fed (Chow; n=7), overnight-fasted (Fasting; n=3), fasted and refed (90 min) (Refeed; n=4), and DIO mice (HFD; n=8). b , UMAP embedding of MBH neurons (>40,000 nuclei; mean 12,401 transcripts per nucleus), with Lepr -expressing neurons labelled by subtype. c , Effects of nutritional manipulations on the total transcriptome of each neuronal population. Expression distance estimate in response to fasting (x-axis) and DIO (y-axis). Data for Lepr neurons is highlighted in cell-type specific colors. Solid diagonal line indicates matched effects between perturbations. d , Leptin gene signature (LGS) expression in for each nutritional manipulations across the indicated subsets of Lepr neurons; HFD (red), refeed (light green), chow (yellow), fasting (dark green)). e , Hierarchical clustering and grouping of differentially expressed genes identified in Lepr/Glp1r neurons. Neuronal activity genes and GABA receptor subunits highlighted.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Expressing, Activity Assay

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a,b , UMAP embedding of mediobasal hypothalamic neurons colored by individual mouse (a) and sequencing batch (b). c , Distribution of UMI counts (top) and genes detected (bottom) per cell across all samples (chow n=7, DIO n=8, fasted n=3, refed n=4). d , UMAP colored by predicted Campbell neuron subtype. e , Mapping confidence scores, with highest confidence in the Lepr/Glp1r population. f , Proportion of cells assigned to each neuronal cluster (n01-n34) across individual samples, showing consistent cluster composition across mice and conditions. g , MINT sPLS-DA projection of three independent leptin treatment transcriptomic datasets used to derive the leptin gene signature (LGS). Fasted/control (blue) and leptin-treated (orange) samples separate along the first two components. h , Gene ontology enrichment of LGS genes, highlighting response to peptide hormone and JAK-STAT signaling among the top terms. i , Model weights for individual LGS genes. j , LGS expression across nutritional states in Tbx19 and Irx3 neurons (***P<0.001). k , Correlation between fasting-induced (y-axis) and DIO-induced (x-axis) log₂ fold changes in AgRP, Lepr/Glp1r, and POMC neurons.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Sequencing, Control, Expressing

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Experimental design of wild-type (WT) mice treated with 3 mg/kg of leptin of saline and sacrificed 1, 3, 6, or 24 hours after injection. MBH nuclei were collected for snRNA-seq. b, Transcriptional distance between cells from leptin treated and control mice. c, LGS changes across Lepr/Glp1r , Pomc and Agrp neurons . d, Overlap between genes induced by acute leptin treatment and those upregulated in DIO in Lepr/Glp1r neurons (93 shared genes; odds ratio=185.3, P =6.28×10⁻²⁴, Fisher’s exact test), indicating that direct leptin action recapitulates a substantial portion of the DIO transcriptional program.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Saline, Injection, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a-c , UMAP embedding of mediobasal hypothalamic neurons from lean mice treated with leptin (3 mg/kg) or saline and harvested at 1, 3, 6, or 24 hours post-injection (n=4-6 per timepoint per group), colored by treatment (a), hours post-injection (b), and sequencing batch (c). d , UMAP colored by neuronal cell type identity, with key Lepr-expressing populations labeled. e , Number of differentially expressed genes (leptin vs saline; adjusted P<0.05) per neuronal population. Red, upregulated; blue, downregulated. f , Volcano plot of leptin-induced differential expression in Lepr/Glp1r neurons. Highlighted genes include canonical leptin targets (blue), immediate early/neuronal activity genes (red), and GABA receptor subunits (green). Dashed line, adjusted P =0.05.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Saline, Injection, Sequencing, Expressing, Labeling, Quantitative Proteomics, Activity Assay

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Lepr/Glp1r neurons constitute ∼78% of all Lepr-expressing GABAergic (Gad1+) input to AgRP (Npy+) neurons, based on reanalysis of published rabies-traced AgRP neuron afferents. Feature plots show expression of Gad1, Glp1r, Npy, and Lepr across traced populations; circled clusters indicate the Lepr/Glp1r population. b,c , UMAP embedding of mediobasal hypothalamic neurons from Glp1r Lepr KO and control mice (35,538 nuclei total), colored by genotype (b) and diet (c) (chow vs DIO; n=6-7 per group). d , UMAP colored by predicted cell type identity (41 clusters) based on label transfer from the nutritional perturbation reference atlas. e , Change in leptin gene signature (LGS) expression in Glp1r Lepr KO relative to control mice across Lepr neuron subtypes (open circles denote P <0.05; linear mixed-effects model).

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Expressing, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Schematic of retrograde rabies tracing from ARC Npy neurons in Lepr Cre-sun1Gfp ;Npy Flp mice. Starter cells (ARC) express TVA and rabies-G via Npy Flp ; rabies-labeled cells are magenta, Lepr -expressing cells green, and co-labeled cells ( Lepr -expressing afferents) show both signals. b, c, Representative images of tissue sections from experiments as in (a). *Indicates viral hit site. Afferent DMH Lepr cells indicated by white arrows. d , Schematic of retrograde rabies tracing from Agrp neurons in Agrp Cre; Glp1r Flp-TDT mice. Rabies-labeled cells are green, Glp1r -expressing cells red, and co-labeled cells ( Glp1r -expressing afferents) show both signals. e, f , Representative images of tissue sections from experiments as in (d); *indicates viral hit site. Rabies-labeled Glp1r afferent cells indicated with white arrows. Scale bars: 200 µm (main images), 100 µm (insets). g , h , Experimental paradigm: Lepr was ablated in Glp1r expressing neurons and animals were fed chow diet ( Agrp , n=7; Glp1r , n=6 Lepr KO and n=6 control) and either sacrificed at 4-5 weeks of age switched onto a HFD for 15 weeks ( Agrp n=2; Glp1r , n=7 Lepr KO and n=6 control) until sacrifice. Mediobasal hypothalami were collected for snRNA-seq. i, Leptin gene signature (LGS) expression in Lepr/Glp1r neurons from for lean (Chow) or DIO Lepr Glp1r KO and control (WT) mice. LGS was significantly reduced in KO neurons (β=−0.087, P <1.0×10⁻⁹; linear mixed-effects model), with a significant genotype × diet interaction ( P =2×10⁻⁹). j, PCA projection of Lepr/Glp1r neurons from DIO Lepr Glp1r KO (red) and Control (blue) mice onto the nutritional perturbation embedding. Centroids for DIO (orange) and fasted (teal) conditions shown as large circles. Lepr Glp1r KO neurons cluster with fasted wild-type neurons (PC1 permutation test, P=0.001), indicating LepR signaling is required to adopt the DIO transcriptional state. k, Volcano plot of differentially expressed genes in Lepr/Glp1r neurons (KO versus WT, DIO). Loss of Lepr abolished the DIO-associated induction of immediate early genes ( Fos , log₂FC=−2.14, adj. P =0.018; Vgf , log₂FC=−1.76, adj. P =1.3×10⁻⁴; Homer1 , log₂FC=−0.66, adj. P =0.027) and reversed the downregulation of GABA receptor subunits ( Gabra3, Gabra4, Gabra5, Gabrb1–b3 ). Dashed line, adjusted P =0.05. See Supplementary Table 7 for full results. l, PCA projection of Agrp neurons from DIO Lepr Glp1r KO (red) and Control (blue) mice; centroids for DIO (orange) and fasted (teal) conditions shown as large circles, as in ( j ). Agrp neurons shift toward the fasted transcriptional state in Lepr Glp1r KO mice (PC1 permutation test, P=0.001), indicating propagation of the transcriptional effect from Lepr/Glp1r neurons. m, Volcano plot of differentially expressed genes in Agrp neurons (KO versus WT, DIO; 128 genes). Genes colored by their response to fasting: orange, fasting-upregulated; blue, fasting-downregulated; grey, neither. Fasting-upregulated genes were enriched among genes increased in KO (OR=8.56, P =1.05×10⁻⁸, Fisher’s exact test), and fasting-downregulated genes were enriched among decreased genes (OR=22.67, P =6.76×10⁻¹⁹), confirming a fasting-like transcriptional state despite obesity.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Labeling, Expressing, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Schematic and representative histology of bilateral AAV-FLEX-FREX-hM3Dq injection into the caudal ARC/ventral DMH of Glp1r-ires-Cre;Trh-p2a-Dre mice. Scale bar: 200 µm. b , Spatial transcriptomics reference map showing the Lepr/Glp1r neuron population (red) targeted by the intersectional DREADD strategy. c , Summary of the DREADD cohort (main text ). d , Baseline characteristics of chow-fed Glp1r Lepr KO (n=20) and control (n=14) mice used for leptin-dependent feeding suppression experiments (main text ). e , Baseline chow-period body weight and DEXA body composition of Glp1r Lepr KO (n=9) and control (n=10) mice prior to HFD exposure . Data are mean ± SD.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Injection, Spatial Transcriptomics, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: Mice containing activating DREADDs in Glp1r/Trh neurons were treated with saline or CNO at the onset of the dark cycle (a), during refeeding following an overnight fast (b), or prior to ghrelin treatment (c). a , Cumulative dark-cycle food intake at 0, 1, 2, and 3 hours following IP CNO or saline in a within-subject crossover design (n=5).. b , Cumulative post-fast food intake at 0, 1, 2, 4, 6, and 8 hours following IP CNO or saline (n=5). c , Cumulative food intake following IP ghrelin with CNO or saline pre-treatment at 0, 1, 2, 4, 6, and 8 hours (n=4). d, Effect of leptin (dark teal) versus saline (light teal) pre-treatment on ghrelin-induced 24-hour food intake in lean Lepr Glp1r KO (KO) and control (WT) mice. Lines connect within-subject measurements (crossover design). e, Cumulative post-fast food intake following leptin (dark teal) or saline (light teal) administration in WT (left) and KO (right) mice. f, g , Body weight (f) and daily food intake (g) before and 7 days after HFD exposure in Lepr Glp1r KO (n=9) and Control (n=10) mice. h , Food intake from (g) separated by dark (top) and light (bottom) cycle. The excess intake in Lepr Glp1r KO mice was concentrated in the dark cycle (genotype × time: χ²(9)=38.33, P =1.52×10⁻⁵). Dashed line indicates HFD switch. All panels: * P <0.05, **P<0.01, ***P<0.001. A-c, e-h: Plotted points represent mean values. Error bars (a-c) and shaded regions (e-h) denote SEM.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Saline, Control

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a,b, Baseline characteristics of Glp1r Lepr KO and control mice used in the chow vs DIO fasting-refeeding experiment (main text ). Chow-fed and DIO cohorts are independent groups of animals. c-e, Baseline characteristics of DIO Glp1r Lepr KO (n=12) and control (n=11) mice used in the ghrelin feeding experiment. c , Summary table including plasma leptin for a subset of mice (KO n=4, WT n=3). d , Individual body weights and ( e ) plasma leptin by genotype, confirming hyperleptinemia in both genotypes. Data are mean ± SD (tables) or mean ± SEM (dot plots) with individual animals shown.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Control, Clinical Proteomics

Journal: bioRxiv

Article Title: A uniquely leptin sensitive hypothalamic neuron population limits hyperphagia and weight gain in diet-induced obesity

doi: 10.64898/2026.03.26.714161

Figure Lengend Snippet: a , Cumulative post-fast food intake (kcal) at 0, 1, 2, 4, and 8 hours in Control (WT, left) and Lepr Glp1r KO (right) mice on chow (light) or HFD (dark). * P <0.05, *** P <0.001. Shaded regions denote SEM. b , Five-hour food intake following IP ghrelin (dark) or saline (light) in DIO WT (n=11) and Lepr Glp1r KO (n=12) mice. Lines connect within-subject measurements (crossover design). ** P <0.01, error bars denote SEM. c , Representative FOS immunofluorescence in the mbARC of DIO Control and Lepr Glp1r KO mice following saline (top) or ghrelin (bottom) injection. 3V, third ventricle; ME, median eminence. d , Quantification of FOS-positive ARC neurons after saline (top; P=0.15) or ghrelin (bottom; P =0.013). Shown are mean-/+ SEM, along with individual data points. e , Left: schematic indicating the mbARC region sampled. Right: representative IBA1 immunofluorescence in DIO WT and Lepr Glp1r KO (KO) mice. f , Quantification of IBA1-positive microglia in the ARC of control (ctrl) and KO mice. Shown are mean-/+ SEM, along with individual data points.

Article Snippet: A Glp1r -specific knockout of Lepr (Lepr Glp1r KO mice) was produced by crossing the Lepr flox mice with Glp1r-ires-Cre mice (Jackson Laboratory, #029283).

Techniques: Control, Saline, Immunofluorescence, Injection

Journal: Translational Psychiatry

Article Title: Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

doi: 10.1038/tp.2016.223

Figure Lengend Snippet: Leptin signaling in the VTA negatively regulates cocaine-conditioned reward and dopamine levels in the NAc. ( a ) Schematic drawing of the AAV -CAG-EGFP-T2A-Cre (left) and the experimental schedule of immunohistochemistry (IHC) and behavior tests after virus injection (right). ( b ) Representative images of the AAV -CAG-EGFP-T2A-Cre -infected VTA from Lepr flox/flox mice and WT littermates. EGFP: green; LepR: red; arrows indicate the EGFP + cells. Scale bar, 100 μm (low-magnification images) and 20 μm (high-magnification images). ( c ) Quantification of the percentage of LepR-positive cells in the EGFP + populations in the VTA of virus-infected Lepr flox/flox mice and WT littermates. ( d ) Concentration of cocaine-induced monoamine neurotransmitters in the NAc (left) and AMG (right) of Lepr flox/flox and WT mice. ( e ) Quantification of the place preference scores of AAV-Cre-injected Lepr flox/flox and WT mice in the pre-test and test sessions. ( f ) Time spent in the open arms of the elevated plus maze (test in the Lepr flox/flox and WT mice. ( g ) Time in the center zone of the open-field test in the Lepr flox/flox and WT mice. The data are presented as the mean±s.e.m. * P <0.05, ** P <0.01. AMG, amygdala; NAc, nucleus accumbens; VTA, ventral tegmental area; WT, wild-type.

Article Snippet: Lepr flox/flox mice, in which exon 1 of the Lepr gene is floxed, were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) (strain name: B6.129P2-Lepr tm1Rck /J ).

Techniques: Immunohistochemistry, Virus, Injection, Infection, Concentration Assay

Journal: Translational Psychiatry

Article Title: Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

doi: 10.1038/tp.2016.223

Figure Lengend Snippet: Leptin signaling in NAc Core negatively regulates cocaine-conditioned reward and is essential for D2R function. ( a ) Representative images of the AAV -CAG-EGFP-T2A-Cre -infected NAc from Lepr flox/flox mice and WT littermates. ( b ) Quantification of the number of LepR-positive cells in the EGFP + cells in the NAc core of virus-infected Lepr flox/flox mice and WT littermates. EGFP: green; LepR: red; arrows indicate the EGFP + cells. Scale bar, 100 μm (low-magnification images) and 20 μm (high-magnification images). ( c ) Quantification of the place preference scores of virus-infected Lepr flox/flox and WT mice in the pre-test and test sessions. ( d ) Schematic of the experimental schedule for cocaine-CPP after cannula implantation (upper panel). Mice received bilateral infusion of the D2R agonist bromocriptine (500 ng) into the NAc core 30 min before cocaine conditioning, and the quantification of the place preference scores in the pre-test and test sessions is shown below. ( e ) Time spent in the open arms of the elevated plus maze test in Lepr flox/flox and WT mice. ( f ) Time in the center zone of the open-field test in the Lepr flox/flox and WT mice. The data are presented as the mean±s.e.m. * P <0.05, ** P <0.01, *** P <0.001. CPP, conditioned preference place; D2R, D2-dopamine receptor; LepR, leptin receptor; NAc, nucleus accumbens; WT, wild-type.

Article Snippet: Lepr flox/flox mice, in which exon 1 of the Lepr gene is floxed, were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) (strain name: B6.129P2-Lepr tm1Rck /J ).

Techniques: Infection, Virus

Journal: Translational Psychiatry

Article Title: Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

doi: 10.1038/tp.2016.223

Figure Lengend Snippet: Leptin signaling in CeA is critical for anxiety but not cocaine-conditioned reward. ( a ) Representative images of the AAV-CAG-EGFP-T2A-Cre -infected CeA from Lepr flox/flox mice and WT littermates. EGFP: green; LepR: red; arrows indicate the EGFP + cells. Scale bar, 100μm (low-magnification images) and 20 μm (high-magnification images). ( b ) Quantification of the percentage of LepR-positive cells in the EGFP + population in the CeA of virus-infected Lepr flox/flox mice and WT mice. ( c ) Quantification of the place preference scores of Lepr flox/flox and WT mice in the pre-test and test sessions. ( d ) Time spent in the open arms of the elevated plus maze test in the Lepr flox/flox and WT mice. ( e ) Time in the center zone of the open-field test in the Lepr flox/flox and WT mice. The data are presented as the mean±s.e.m. * P <0.05, ** P <0.01, *** P <0.001. CeA, central amygdala; LepR, leptin receptor; WT, wild-type.

Article Snippet: Lepr flox/flox mice, in which exon 1 of the Lepr gene is floxed, were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) (strain name: B6.129P2-Lepr tm1Rck /J ).

Techniques: Infection, Virus

Journal: Translational Psychiatry

Article Title: Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

doi: 10.1038/tp.2016.223

Figure Lengend Snippet: Upregulated leptin signaling reduces cocaine-CPP. ( a , b ) Mice received injection of saline or leptin (1 mg kg −1 i.p.) 30 min before conditioning, and the quantification of the place preference scores in the pre-test and test sessions is shown. ( c ) Schematic of the saccharin reward experimental schedule. Three groups of mice were confined to the apparatus for a 1-h operant task for 12 days to receive water (W) or saccharin daily (CS) or saccharin only on the last session (AS). The mice were decapitated 24 h after the last session. ( d , e ) The levels of LepR mRNA ( d ), pSTAT3 protein and total STAT3 ( e ) in the NAc and VTA were detected. Images are representative of similar results from five to six independent individuals. ( f ) Schematic of the operant task and cocaine-CPP schedule. Three groups of mice (W, AS and CS) performed a 1 h operant task for 12 days, and 24 h after the last session, each mouse received cocaine-context conditioning learning. Place preference was examined 24 h later. ( g ) Quantification of the place preference scores of the three groups of mice in the pre-test and test sessions. ( h ) Schematic of the modified cocaine-CPP schedule. SMLA (500 ng) or vehicle was infused into the NAc or VTA 30 min after saccharin administration, and the mice received cocaine-context conditioning 24 h later. ( i , j ) Quantification of the place preference scores of mice receiving SMLA (500 ng) infusion into the NAc ( i ) or VTA ( j ) after saccharin administration in the pre-test and test sessions. The data are presented as the mean±s.e.m. * P <0.05, ** P <0.01. CPP, conditioned place preference; NAc, nucleus accumbens; SMLA, superactive mouse leptin antagonist; VTA, ventral tegmental area.

Article Snippet: Lepr flox/flox mice, in which exon 1 of the Lepr gene is floxed, were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) (strain name: B6.129P2-Lepr tm1Rck /J ).

Techniques: Injection, Saline, Modification, Conditioned Place Preference