Cited by 370Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionStress Responses and Cortisol

The DOI matches its Crossref record; 165 of the 170 references it cites were found in a registry or an index.

The flinders sensitive line rats: A genetic animal model of depression

Overstreet, David H.·1993·Neuroscience & Biobehavioral Reviews

Open this paper in CoChat — free account

Abstract

The Flinders Sensitive Line (FSL) rat, selectively bred for increased responses to the anticholinesterase DFP, was originally proposed as an animal model of depression because, like depressed humans, it is supersensitive to the behavioral and hormonal effects of cholinergic (muscarinic) agonists. The present review critically examines earlier and recent data collected on FSL rats to assess whether the model has good face, construct and/or predictive validity. With respect to face validity, FSL rats resemble depressed humans, at least superficially, in that they demonstrate: (a) reduced locomotor activity, (b) reduced body weight, (c) increased REM sleep, and (d) cognitive (learning) difficulties. So far, studies designed to assess the presence of anhedonia, a cardinal symptom of melancholic depression, have been inconclusive, but there are trends for the FSL rats to be more anhedonic than their control counterparts, the Flinders Resistant Line (FRL) rats, when exposed to chronic mild stress. Thus, FSL rats fulfill the criterion of face validity. Because FSL rats also are more sensitive to cholinergic agonists and have phase advanced circadian rhythms, they meet the criteria for the cholinergic and circadian rhythm models of depression and, therefore, have good construct validity. A key behavioral symptom exhibited by the FSL rat is demonstration of an exaggerated immobility when exposed to stressors such as foot shock and forced swimming. This behavioral abnormality has been normalized by a number of well-recognized antidepressant drugs such as imipramine and desipramine, as well as newer generation antidepressants with promising clinical effects such as sertraline and rolipram. However, several treatments that have not been routinely used to treat depression (lithium, exposure to bright light, the anticholinesterase DFP) have been ineffective in reversing the exaggerated immobility. Thus, the evidence in the present review indicates that the FSL rat model of depression fulfills the criteria of face, construct, and predictive validities.

Integrity signals

Registry

Crossref · 10.1016/s0149-7634(05)80230-1

Cites

165 of 165 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat
Pellow, S., Chopin, P., File, S. E., & Briley, M. (1985) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(85)90031-7 · Cited by 5,822
Mood and memory
Bower, G. H. (1981) · American Psychologist · doi:10.1037/0003-066x.36.2.129 · Cited by 4,154
THE CATECHOLAMINE HYPOTHESIS OF AFFECTIVE DISORDERS: A REVIEW OF SUPPORTING EVIDENCE
Schildkraut, J. J. (1965) · American Journal of Psychiatry · doi:10.1176/ajp.122.5.509 · Cited by 3,568
Psychopharmacology: The third generation of progress
O’Connell, R. A. (1988) · Comprehensive Psychiatry · doi:10.1016/0010-440x(88)90057-0 · Cited by 3,020
Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant
Willner, P., Towell, A., Sampson, D., Sophokleous, S., & Muscat, R. (1987) · Psychopharmacology · doi:10.1007/bf00187257 · Cited by 1,993
The validity of animal models of depression
Willner, P. (1984) · Psychopharmacology · doi:10.1007/bf00427414 · Cited by 1,404
The Biochemistry of Affective Disorders
Coppen, A. (1967) · British Journal of Psychiatry · doi:10.1192/bjp.113.504.1237 · Cited by 1,230
A cholinergic-adrenergic hypothesis of mania and depression
Janowsky, D., Davis, J., El-Yousef, M. K., & Sekerke, H. J. (1972) · The Lancet · doi:10.1016/s0140-6736(72)93021-8 · Cited by 1,134
Is the forced swimming test a suitable model for revealing antidepressant activity?
Borsini, F., & Meli, A. (1988) · Psychopharmacology · doi:10.1007/bf00176837 · Cited by 1,053
Catecholamine theories of reward: A critical review
Wise, R. A. (1978) · Brain Research · doi:10.1016/0006-8993(78)90253-6 · Cited by 788

Show all 170 references

Research works printed but not linked: 5

Horowski, 1985, Clinical effects of the neurotropic-selective cAMP phosphodiesterase inhibitor rolipram in depressed patients: Global evaluation of preliminary reports, Curr. Ther. Res., 38, 23
Maier, 1984, Learned helplessness and animal models of depression. Prog Neuropsychopharmacol, Biol. Psychiatry, 8, 435
Risch, 1981, Differential mood effects of arecoline in depressed patients and normal volunteers, Psychopharmacol. Bull., 19, 696
Shiromani, 1990, Dietary lithium blunts oxotremorine-induced hypothermia in a genetic animal model of depression, Lithium, 1, 186
Shiromani, 1990, Failure of dietary lithium to alter immobility in an animal model of depression, Lithium, 1, 241

Sorted by citations

Items 101–200 of 370

Regulation of phosphodiesterase-4 (PDE4) expression in mouse brain by repeated antidepressant treatment: Comparison with rolipram
Dlaboga, D., HajjHussein, H., & O’Donnell, J. M. (2006) · Brain Research · doi:10.1016/j.brainres.2006.04.032 · Cited by 72
“In rats, they suppress muricidal behavior in olfactory bulbectomized rats (Mizokawa et al., 1988),reduce the time of immobility inthe forced-swim test ( Overstreet, 1993 ), and reduce response rate and increase reinforcement rate under a differential-reinforcement-of-low-rate (DRL) schedule (O'Donnell, 1993).”
Background
The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder
Malki, K., Keers, R., Tosto, M. G., Lourdusamy, A., Carboni, L., Domenici, E., Uher, R., McGuffin, P., & Schalkwyk, L. C. (2014) · BMC Medicine · doi:10.1186/1741-7015-12-73 · Cited by 74
“anticholinesterase diisopropyl fluorophosphates (DFP) treatment [24].”
Effect of chronic antidepressant treatment on responses to apomorphine in selectively bred rat strains
Puciłowski, O., & Overstreet, D. H. (1993) · Brain Research Bulletin · doi:10.1016/0361-9230(93)90293-k · Cited by 72
The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease
Lee, J. G., Woo, Y. S., Park, S. W., Seog, D., Seo, M. K., & Bahk, W. (2019) · Brain Sciences · doi:10.3390/brainsci9100285 · Cited by 72
“The Flinders Sensitive Line (FSL) rat was originally proposed as an animal model of depression because, like depressed humans, it is supersensitive to the behavioral and hormonal effects of cholinergic (muscarinic) agonists [78].”
Background
Targeting metabotropic glutamate receptors for the treatment of depression and other stress-related disorders
Dogra, S., & Conn, P. J. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108687 · Cited by 71
Chronic mild stress has no effect on responding by rats for sucrose under a progressive ratio schedule
Barr, A. M., & Phillips, A. G. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00060-2 · Cited by 71
Depressive Characteristics of FSL Rats
Tizabi, Y., Rezvani, A. H., Russell, L. T., Tyler, K. Y., & Overstreet, D. H. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00236-7 · Cited by 70
Self-citation
Antidepressant Effect of Ingested Nicotine in Female Rats of Flinders Resistant and Sensitive Lines
Djurić, V. J., Dunn, E., Overstreet, D. H., Dragomir, A., & Steiner, M. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00091-8 · Cited by 79
Stress-based animal models of depression: Do we actually know what we are doing?
Yin, X., Gueven, N., & Dietis, N. (2016) · Brain Research · doi:10.1016/j.brainres.2016.09.027 · Cited by 75
“Since only about 10–50% of rodents successfully develop depressive-like symptoms (Overstreet, 1993), the use of strains that are vulnerable to stress could increase the face validity of animal models of depression.”
Background
Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur, Y. S., Mose, T. N., Blakeman, S., & Picciotto, M. R. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13769 · Cited by 71
“Similarly, a genetic animal model of depression selectively bred for its sensitivity to cholinergic agents (the Flinders sensitive rat strain) shows increased ACh levels and exhibits behaviours resembling symptoms of depression (Overstreet, 1993).”
Background
Running has Differential Effects on NPY, Opiates, and Cell Proliferation in an Animal Model of Depression and Controls
Bjørnebekk, A., Mathé, A. A., & Brené, S. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300820 · Cited by 69
“Subsequently, it was realized that FSL exhibits a phenotype that mimics a number of symptoms seen in human depression (Husum et al, 2001; Overstreet, 1993; Pucilowski et al, 1993).”
Background
Antidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depression
Liebenberg, N., Harvey, B. H., Brand, L., & Brink, C. B. (2010) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32833befe5 · Cited by 67
“…are innately more immobile in the forced swim test (FST) than Flinders resistant line (FRL) control rats and display a decrease in immobility after chronic, but not acute, antidepressant treatment (Overstreet, 1993, 2002), therefore more closely resembling the clinical scenario in humans.”
Background
Effects of melatonin receptor ligands on swim test immobility
Overstreet, D. H., Puciłowski, O., Retton, M.-C., Delagrange, P., & Lemaître, B. J. (1998) · Neuroreport · doi:10.1097/00001756-199801260-00014 · Cited by 67
VTA Dopamine Neuron Bursting is Altered in an Animal Model of Depression and Corrected by Desipramine
Friedman, A., Friedman, Y., Dremencov, E., & Yadid, G. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-9016-8 · Cited by 63
“…characteristic of depression such as reduced locomotion, reduced activity in the swim test, increased anhedonia in response to chronic mild stress, increased amount and reduced onset of rapid eye movement sleep, cognitive difficulties, and reduced body weight (for review see Overstreet 1993).”
Background
Role of serotonin (5-HT) in the antidepressant-like properties of neuropeptide Y (NPY) in the mouse forced swim test
Redrobe, J. P., Dumont, Y., Fournier, A., Baker, G. B., & Quirion, R. (2005) · Peptides · doi:10.1016/j.peptides.2005.03.029 · Cited by 65
Changes in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography
Hannestad, J. O., Cosgrove, K. P., DellaGioia, N. F., Perkins, E., Bois, F., Bhagwagar, Z., Seibyl, J. P., McClure-Begley, T. D., Picciotto, M. R., & Esterlis, I. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.04.004 · Cited by 63
“Rats bred for increased sensitivity to cholinergic agents show behaviors that resemble symptoms of depression, such as lethargy, reductions in self-stimulation, and increased behavioral despair (12).”
Background
Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: Mechanism of action and possible interactions with cholinergic system
Kruk-Słomka, M., Michalak, A., & Biała, G. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.01.051 · Cited by 64
Selectively Bred Rodents as Models of Depression and Anxiety
Wegener, G., Mathé, A. A., & Neumann, I. D. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_192 · Cited by 65
Relaxin’ the brain: a case for targeting the nucleus incertus network and relaxin‐3/RXFP3 system in neuropsychiatric disorders
Kumar, J. R., Rajkumar, R., Jayakody, T., Marwari, S., Hóng, J., Ma, S., Gundlach, A. L., Lai, M. K. P., & Dawe, G. S. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13564 · Cited by 63
“Similarly, the Flinders sensitive line (FSL) of rats were developed through selective breeding to exhibit cholinergic supersensitivity, a feature seen in depressed patients (Overstreet, 1993).”
The antidepressant activity of inositol in the forced swim test involves 5-HT2 receptors
Einat, H., Clénet, F., Shaldubina, A., Belmaker, R. H., & Bourin, M. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00314-4 · Cited by 64
“Similar effects were also reported recently in a variety of animal models of depression where inositol administration to rats was demonstrated to reduce reserpine-induced hypoactivity, immobility time in the forced swim test [9] and to counter the innate immobility of Flinders sensitive line rats, a genetic model of d…”
Brain 5-HT synthesis in the Flinders Sensitive Line rat model of depression: An autoradiographic study
Hasegawa, S., Nishi, K., Watanabe, A., Overstreet, D. H., & Dikšić, M. (2006) · Neurochemistry International · doi:10.1016/j.neuint.2005.11.012 · Cited by 62
“Indeed, the differences in 5-HT synthesis between the FSL and FRL rats, and the FRL and SD rats suggest that the imbalance is less pronounced in the FRL rats, which is supported by their behavioural characteristics (Overstreet, 1993).”
Background
Altered fecal microbiota composition in the Flinders sensitive line rat model of depression
Tillmann, S., Abildgaard, A. M., Winther, G., & Wegener, G. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5094-2 · Cited by 60
“…significantly less than FRL rats at both baseline (day 0; means ± SD, 301.6 ± 28.2 g vs. 354.0 ± 34.1 g; F(1,42) = 32.97, p < 0.001) and endpoint (day 17; 340.0 ± 27.1 g vs. 397.7 ± 34.6 g; F(1,42) = 39.51, p < 0.001), which is characteristic for their depressive-like phenotype (Overstreet, 1993).”
Influential
Adaptations in reward-related behaviors and mesolimbic dopamine function during motherhood and the postpartum period
Rincón‐Cortés, M., & Grace, A. A. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100839 · Cited by 67
“The Flinders Sensitive Line (FSL), which was selectively bred from Sprague Dawley (SD) rats, and Wistar Kyoto (WKY) strain, which was selectively bred from Wistar rats, are considered genetic animal models relevant for the study of endogenous depression and PPD [187; 188; 189].”
Method
The β-Endorphin Role in Stress-Related Psychiatric Disorders
Wagner, A. M., Dikshtein, Y., & Yadid, G. (2009) · Current Drug Targets · doi:10.2174/138945009789735147 · Cited by 59
“(xviii) FSL rats [135].”
Changed Concentrations of Tachykinins and Neuropeptide Y in Brain of a Rat Model of Depression Lithium Treatment Normalizes Tachykinins
Husum, H. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00198-6 · Cited by 59
“These include reduced bodyweight, reduced locomotor activity, increased rapid eye movement (REM) sleep and cognitive deficits (Overstreet 1993; Yadid et al. 2000).”
BackgroundInfluential
Psychotropic and neurotropic activity
Vogel, H. G., & Vogel, W. H. (1997) · Springer eBooks · doi:10.1007/978-3-662-03333-3_5 · Cited by 61
Antidepressant-like effects of the vasopressin V1b receptor antagonist SSR149415 in the Flinders Sensitive Line rat
Overstreet, D. H., & Griebel, G. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.07.021 · Cited by 58
Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression
Vieyra-Reyes, P., Mineur, Y. S., Picciotto, M. R., Túnez, I., Vidaltamayo, R., & Drucker-Colı́n, R. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2008.05.007 · Cited by 59
Cholinergic/Serotonergic Interactions in Hypothermia: Implications for Rat Models of Depression
Overstreet, D. H., Daws, L. C., Schiller, G. D., Orbach, J., & Janowsky, D. S. (1998) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)00514-5 · Cited by 57
Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic study
Watanabe, A., Tohyama, Y., Nguyen, K. Q., Hasegawa, S., Debonnel, G., & Dikšić, M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01702.x · Cited by 56
Cholinergic pathways modulate experimental dinitrobenzene sulfonic acid colitis in rats
Miceli, P. C., & Jacobson, K. (2003) · Autonomic Neuroscience · doi:10.1016/s1566-0702(03)00023-7 · Cited by 56
“hypothermia and locomotor activity) to cholinergic agonists, and have elevated muscarinic receptors in several brain regions, whereas the response of Flinder’s Resistant Line rats to cholinergic agonists is similar to randomly bred Sprague–Dawley rats (Overstreet et al., 1988; Overstreet, 1993).”
BackgroundResult
Opioid receptor modulation of neural circuits in depression: What can be learned from preclinical data?
Puryear, C. B., Brooks, J. M., Tan, L. A., Smith, K. L., Li, Y., Cunningham, J. I., Todtenkopf, M. S., Dean, R. L., & Sánchez, C. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.12.007 · Cited by 60
“Two such strains are the Flinders sensitive line and Wistar-Kyoto (WKY) rats, and each exhibits enhanced reactions to stress and impaired stress-coping behaviors (Overstreet, 1993; Willner and Belzung, 2015).”
Effects of antidepressants on the performance in the forced swim test of two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions
Piras, G., Giorgi, O., & Corda, M. G. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1904-x · Cited by 58
“A number of reports, however, have shown effects of antidepressant drugs in the forced swim test after chronic treatment with doses that were inactive when given acutely (Dulawa et al. 2004; Cryan et al. 2005a; Pucilowski and Overstreet 1993).”
BackgroundMethodInfluential
Probiotics Affect One‐Carbon Metabolites and Catecholamines in a Genetic Rat Model of Depression
Tillmann, S., Awwad, H. M., Eskelund, A., Treccani, G., Geisel, J., Wegener, G., & Obeid, R. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201701070 · Cited by 52
The Neurobiology of Depression: Perspectives from Animal and Human Sleep Studies
Shaffery, J. P., Hoffmann, R. F., & Armitage, R. (2003) · The Neuroscientist · doi:10.1177/1073858402239594 · Cited by 55
“…of Flinders, Australia) is one of the earliest (Overstreet and Russell 1982; Russell and others 1982; Overstreet 1986) and best studied line of animals specifically bred as a genetic animal model of depression (for a review, see Overstreet 1993; Overstreet and others 1995; Yadid and others 2000).”
BackgroundInfluential
Potential therapeutic uses of mecamylamine and its stereoisomers
Nickell, J. R., Grinevich, V. P., Siripurapu, K. B., Smith, A. M., & Dwoskin, L. P. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.04.005 · Cited by 55
“…antidepressant-like effects of nicotine is supported also by findings that acute mecamylamine reverses these antidepressant-like effects of nicotine in the Flinders Sensitive Line (FSL) of rats (Tizabi et al., 2000), another animal model of depression (Overstreet, 1993; Overstreet et al., 1995).”
Result
Resting Glutamate Levels and Rapid Glutamate Transients in the Prefrontal Cortex of the Flinders Sensitive Line Rat: A Genetic Rodent Model of Depression
Hascup, K. N., Hascup, E. R., Humeidan, M., Glaser, P. E. A., Yoshitake, T., Mathé, A. A., Gerhardt, G. A., & Kehr, J. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.60 · Cited by 53
“Studies of mature (3-month-old) FSL rats support decreased appetite and weight when compared with control, Flinders Resistant Line (FRL) rats (Overstreet, 1993).”
Background
Confirmation of antidepressant potential of the selective β3 adrenoceptor agonist amibegron in an animal model of depression
Overstreet, D. H., Stemmelin, J., & Griebel, G. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.02.020 · Cited by 53
A prescription to resist proscriptions for murine models of depression
Lucki, I. (2000) · Psychopharmacology · doi:10.1007/s002130000561 · Cited by 55
Biological basis for the co-morbidity between smoking and mood disorders
Mineur, Y. S., & Picciotto, M. R. (2009) · Journal of Dual Diagnosis · doi:10.1080/15504260902869964 · Cited by 51
“FSL rats are more sensitive to cholinesterase inhibitors and show a constellation of depression-like phenotypes (Overstreet, 1993).”
Background
Quantitative hippocampal structural changes following electroconvulsive seizure treatment in a rat model of depression
Kaae, S. S., Chen, F., Wegener, G., Madsen, T. M., & Nyengaard, J. R. (2012) · Synapse · doi:10.1002/syn.21553 · Cited by 52
Abnormal patterns of maternal behavior in a genetic animal model of depression
Lavi‐Avnon, Y., Yadid, G., Overstreet, D. H., & Weller, A. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.02.006 · Cited by 51
The dose makes the poison: From glutamate-mediated neurogenesis to neuronal atrophy and depression
Rubio-Casillas, A., & Fernández-Guasti, A. (2016) · Reviews in the Neurosciences · doi:10.1515/revneuro-2015-0066 · Cited by 49
“The depressive-like behavior of Flinders sensitive line (FSL) rats, a genetic animal model of depression ( Overstreet, 1993), is associated with a selective epigenetically induced down-regulation of mGluR2.”
Background
Defective group-II metaboropic glutamate receptors in the hippocampus of spontaneously depressed rats
Matrisciano, F., Caruso, A., Orlando, R., Marchiafava, M., Bruno, V., Battaglia, G., Gruber, S. H. M., Melchiorri, D., Tatarelli, R., Girardi, P., et al. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.05.014 · Cited by 50
“We decided to use flinders sensitive line (FSL) rats that show a spontaneous depressive phenotype, as reflected by an increased immobility time at the forced swim test (Overstreet, 1993).”
Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation
Hadar, R., Dong, L., Del-Valle-Anton, L., Güneykaya, D., Voget, M., Edemann-Callesen, H., Schweibold, R., Djodari-Irani, A., Goetz, T., Ewing, S. G., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.12.003 · Cited by 56
“…properties underlies the therapeutic effect of neuromodulation in general or whether it reflects an intrinsic feature of the MIA model, we conducted an additional study in a genetic model of depression - the Flinders Sensitive rat Line (FSL) (Overstreet, 1993; Overstreet and Russell, 1982).”
Homeostatic Regulation of Sleep in a Genetic Model of Depression in the Mouse: Effects of Muscarinic and 5-HT1A Receptor Activation
Popa, D., Yacoubi, M. E., Vaugeois, J., Hamon, M., & Adrien, J. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300948 · Cited by 49
“Neuropsychopharmacology reported for other animal models of depression (Overstreet, 1993; Solberg et al, 2001) and are reminiscent of the behavioural inhibition and the global flattening of circadian rhythms observed in depressed patients (Bunney and Bunney, 2000; Souetre et al, 1989).”
BackgroundInfluential
Increased Basal REM Sleep But No Difference in Dark Induction or Light Suppression of REM Sleep in Flinders Rats with Cholinergic Supersensitivity
Benca, R. M. (1996) · Neuropsychopharmacology · doi:10.1016/0893-133x(95)00154-6 · Cited by 49
Corticotropin-releasing factor type-1 receptor antagonists: The next class of antidepressants?
Nielsen, D. M. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.06.003 · Cited by 50
Anxiety-like behaviors in pre-pubertal rats of the Flinders Sensitive Line (FSL) and Wistar-Kyoto (WKY) animal models of depression
Braw, Y., Malkesman, O., Dagan, M., Bercovich, A., Lavi‐Avnon, Y., Schroeder, M., OVERSTREET, D., & Weller, A. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.09.013 · Cited by 49
Escitalopram reduces circulating pro-inflammatory cytokines and improves depressive behavior without affecting sleep in a rat model of post-cardiac infarct depression
Bah, T. M., Benderdour, M., Kaloustian, S., Karam, R., Rousseau, G., & Godbout, R. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.07.039 · Cited by 47
Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity
Overstreet, D. H., Miller, C. S., Janowsky, D. S., & Russell, R. W. (1996) · Toxicology · doi:10.1016/0300-483x(96)03370-7 · Cited by 48
“It is particularly noteworthy that the FSL rats are more sensitive to both alcohol (Overstreet et al., 1990b) and nicotine (Schiller and Overstreet, 1993).”
BackgroundResultInfluential
Anti-Anhedonic Effect of Deep Brain Stimulation of the Prefrontal Cortex and the Dopaminergic Reward System in a Genetic Rat Model of Depression: An Intracranial Self-Stimulation Paradigm Study
Rea, E., Rummel, J., Schmidt, T. T., Hadar, R., Heinz, A., Mathé, A. A., & Winter, C. (2013) · Brain stimulation · doi:10.1016/j.brs.2013.09.002 · Cited by 52
“They were selectively bred for hypersensitivity to a cholinergic agent over multiple generations and have been found to display several depressive-like symptoms, such as passive stress coping, reduced appetite, elevated REM sleep, HPA axis as well as neuropeptide Y system dysregulation [23].”
Background
Are neuropeptides relevant for the mechanism of action of SSRIs?
Gołyszny, M. J., & Obuchowicz, E. (2019) · Neuropeptides · doi:10.1016/j.npep.2019.02.002 · Cited by 48
The reward system and maternal behavior in an animal model of depression: a microdialysis study
Lavi‐Avnon, Y., Weller, A., Finberg, J. P. M., Gispan-Herman, I., Kinor, N., Stern, Y., Schroeder, M., Gelber, V., Bergman, S. Y., Overstreet, D. H., et al. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0961-2 · Cited by 46
“…or chronic exposure to stressors, FSL male rats exhibited a greater decrease in saccharin intake compared to controls (Ayensu et al. 1995; Pucilowski et al. 1993) and were considered to have stress-induced anhedonia (Pucilowski et al. 1993; see also Overstreet 1993, 2002; Overstreet et al. 2005).”
BackgroundResultInfluential
Alpha-melanocyte stimulating hormone antagonizes antidepressant-like effect of neuropeptide Y in Porsolt's test in rats
Goyal, S. N., Kokare, D. M., Ct, C., & Subhedar, N. K. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.09.004 · Cited by 46
Altered gene expression for catecholamine biosynthetic enzymes and stress response in rat genetic model of depression
Serova, L. I., Sabban, E. L., Zangen, A., Overstreet, D. H., & Yadid, G. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00270-8 · Cited by 46
Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features
van Enkhuizen, J., Milienne-Petiot, M., Geyer, M. A., & Young, J. W. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4000-4 · Cited by 46
“Early observations in animals support depression-relevant behavior in a selectively bred line of rats with increased sensitivity to acetylcholinesterase (AChE; the primary enzyme hydrolyzing ACh), the Flinders Sensitive Line (Overstreet 1993).”
Background
The role of the hippocampus in mediating emotional responses to nicotine and cannabinoids: a possible neural substrate for functional interactions
Viveros, M., Marco, E. M., Llorente, R., & Lamota, L. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282d28fb4 · Cited by 44
“…aspects of the endocannabinoid system is beyond the scope of this paper, but the reader can find excellent comprehensive reviews (e.g. De Petrocellis et al., 2004; Bisogno et al., 2005; Ligresti et al., 2005; Bari et al., 2006; Matias and Di Marzo, 2006; Pacher et al., 2006, Pagotto et al., 2006).”
Background
Expression Profiling of a Genetic Animal Model of Depression Reveals Novel Molecular Pathways Underlying Depressive-Like Behaviours
Blaveri, E., Kelly, F., Mallei, A., Harris, K., Taylor, A. R., Reid, J. L., Razzoli, M., Carboni, L., Piubelli, C., Musazzi, L., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012596 · Cited by 44
“These data are in line with the higher sensitivity to cholinergic agonists of FSL with respect to FRL animals [3,5,21], and consistent with a depression model mimicking the cholinergic supersensitivity observed in depressed patients [22,29].”
Result
5-HT1A receptor subsensitivity in infancy and supersensitivity in adulthood in an animal model of depression
Shayit, M., Yadid, G., Overstreet, D. H., & Weller, A. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02944-5 · Cited by 43
Bipolar disorder: candidate drug targets
Zarate, C. A., & Manji, H. K. (2008) · Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20042 · Cited by 42
Nerve growth factor (NGF) has novel antidepressant-like properties in rats
Overstreet, D. H., Fredericks, K., Knapp, D., Breese, G., & McMichael, J. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.11.010 · Cited by 42
“The FSL rat is innately more immobile in the forced swim test than its control counterpart, the Flinders Resistant Line (FRL) rat, and exhibits a decrease in immobility following chronic, but not acute, treatment with desipramine (DMI) or sertraline (Pucilowski and Overstreet, 1993).”
BackgroundMethod
Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test
Addy, N. A., Nunes, E. J., & Wickham, R. J. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.04.002 · Cited by 42
Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery
McArthur, R. A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.02.004 · Cited by 42
Pre-clinical models of reward deficiency syndrome: A behavioral octopus
Gondré‐Lewis, M. C., Bassey, R. B., & Blum, K. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.021 · Cited by 42
“The Flinders Sensitive rat line (FSL), like WKY, is an accepted animal model of depression characterized by decreased locomotor activity, increased rapid eye movement sleep and exaggerated immobility with the forced swim test (Overstreet and Wegener, 2013, Overstreet, 1993).”
Background
Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression
Hildreth, C. M., Padley, J. R., Pilowsky, P. M., & Goodchild, A. K. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01009.2007 · Cited by 42
Effects of maternal separation on neuropetide Y and calcitonin gene-related peptide in “depressed” Flinders Sensitive Line rats: A study of gene–environment interactions
Wörtwein, G., Husum, H., Andersson, W., Bolwig, T. G., & Mathé, A. A. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.01.027 · Cited by 42
Decreased limbic vesicular monoamine transporter 2 in a genetic rat model of depression
Schwartz, K., Yadid, G., Weizman, A., & Rehavi, M. (2003) · Brain Research · doi:10.1016/s0006-8993(02)04167-7 · Cited by 42
Electroconvulsive stimuli alter nerve growth factor but not brain-derived neurotrophic factor concentrations in brains of a rat model of depression
Angelucci, F., Aloe, L., Jiménez-Vasquez, P., & Mathé, A. A. (2003) · Neuropeptides · doi:10.1016/s0143-4179(03)00004-0 · Cited by 42
The effects of long-term administration of rubidium or lithium on reactivity to stress and on dopamine output in the nucleus accumbens in rats
Gambarana, C., Ghiglieri, O., Masi, F., Scheggi, S., Tagliamonte, A., & Montis, M. G. D. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01286-x · Cited by 42
Targeting the Noradrenergic System for Gender-Sensitive Medication Development for Tobacco Dependence
Verplaetse, T. L., Weinberger, A. H., Smith, P. H., Cosgrove, K., Mineur, Y. S., Picciotto, M. R., Mazure, C. M., & McKee, S. A. (2015) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntu280 · Cited by 41
Pharmacological Features of Masculine Sexual Behavior in an Animal Model of Depression
Bonilla‐Jaime, H., Retana‐Márquez, S., & Velázquez‐Moctezuma, J. (1998) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)00484-x · Cited by 40
Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System
Edemann-Callesen, H., Voget, M., Empl, L., Vogel, M., Wieske, F., Rummel, J., Heinz, A., Mathé, A. A., Hadar, R., & Winter, C. (2015) · Brain stimulation · doi:10.1016/j.brs.2015.02.009 · Cited by 44
“Intracranial self-stimulation: The curve-shift variant of the ICSS-paradigm was used [42] and conducted in an operant chamber equipped with a lever (TSE Systems, Bad Homburg, Germany).”
BackgroundResultInfluential
Neuromodulation, Emotional Feelings and Affective Disorders
Pereira, A., & Wang, F. (2015) · Mens Sana monographs · doi:10.4103/0973-1229.154533 · Cited by 40
“Pet1 is specifically expressed in the 5-HT neurons and directly activates the transcription of genes implicated in the serotonergic machinery.[73] Compared to WT and Pet +/− littermates, Pet −/−mice have an 80% reduction in 5-HT tissue levels, with no significant changes in the levels of DA (Hendricks et al.”
BackgroundResult
Hypothesis linking the noradrenergic and dopaminergic systems in depression
Weiss, J. M., Demetrikopoulos, M. K., West, C. H. K., & Bonsall, R. W. (1995) · Depression · doi:10.1002/depr.3050030503 · Cited by 40
Experimental hypothyroidism increases immobility in rats in the forced swim paradigm
Kulikov, A. V., Torrésani, J., & Jeanningros, R. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00664-2 · Cited by 39
Rats selectively-bred for behavior related to affective disorders: Proclivity for intake of alcohol and drugs of abuse, and measures of brain monoamines
Weiss, J. M., West, C. H. K., Emery, M., Bonsall, R. W., Moore, J. P., & Boss-Williams, K. A. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.09.027 · Cited by 39
Prenatal stress effects on emotion regulation differ by genotype and sex in prepubertal rats
Schroeder, M., Sultany, T., & Weller, A. (2012) · Developmental Psychobiology · doi:10.1002/dev.21010 · Cited by 42
The Role of Muscarinic Receptors in the Pathophysiology of Mood Disorders:A Potential Noveltreatment?
Jeon, W. J., Dean, B., Scarr, E., & Gibbons, A. S. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150612230045 · Cited by 38
“Significantly, this strain of rat was developed by the selective breeding of Sprague-Dawley (SD) rats for high sensitivity to anticholinesterase [57-59].”
Background
Probiotics reduce risk-taking behavior in the Elevated Plus Maze in the Flinders Sensitive Line rat model of depression
Tillmann, S., & Wegener, G. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.08.025 · Cited by 35
“001), which is characteristic for their depressive-like phenotype [38].”
Decoding of dopaminergic mesolimbic activity and depressive behavior
Friedman, A., Yadid, G., Roth‐Deri, I., Dremencov, E., Friedman, Y., Goutkin, S., Kravchinsky, E., Mintz, M., Levi, D., & Overstreet, D. H. (2007) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-0016-5 · Cited by 38
“These rats exhibit behavioral features characteristic of depression, such as reduced locomotion, reduced activity in the swim test, increased anhedonia in response to chronic mild stress, increased amount and reduced onset of REM (rapid eye movement) sleep, cognitive difficulties, and reduced body weight (for review s…”
Background
Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat
Pereira, M., Farrar, A. M., Hockemeyer, J., Müller, C. E., Salamone, J. D., & Morrell, J. I. (2010) · Psychopharmacology · doi:10.1007/s00213-010-2015-4 · Cited by 37
“Moreover, postpartum Flinders sensitive line (FSL) female rats, a genetic animal model of depression (Overstreet 1993), showed reduced expression of active maternal behaviors correlated with reduced accumbens DA release while interacting with their pups compared to control mother rats (Lavi-Avnon…”
S-Ketamine Rapidly Reverses Synaptic and Vascular Deficits of Hippocampus in Genetic Animal Model of Depression
Ardalan, M., Wegener, G., Rafati, A. H., & Nyengaard, J. R. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw098 · Cited by 39
“A total of 24 male Flinders Sensitive Line (FSL; a highly validated genetic animal model of depression with good face, construct, and predictive validities) (Overstreet, 1993; Wegener et al., 2012) and Flinders Resistant Line (FRL) rats as control group were used in this study.”
Method
Genetically Transmitted Cholinergic Hyperresponsiveness Predisposes to Experimental Asthma
DJURIĆ, V. J., Cox, G., Overstreet, D. H., Smith, L. A., Dragomir, A., & Steiner, M. S. (1998) · Brain Behavior and Immunity · doi:10.1006/brbi.1998.0538 · Cited by 37
Neuropeptide Y modulates the antidepressant activity of imipramine in olfactory bulbectomized rats: Involvement of NPY Y1 receptors
Goyal, S. N., Upadhya, M. A., Kokare, D. M., Bhisikar, S. M., & Subhedar, N. K. (2009) · Brain Research · doi:10.1016/j.brainres.2009.02.033 · Cited by 36
Exacerbated loss of cell survival, neuropeptide Y‐immunoreactive (IR) cells, and serotonin‐IR fiber lengths in the dorsal hippocampus of the aged flinders sensitive line “depressed” rat: Implications for the pathophysiology of depression?
Husum, H., Aznar, S., Høyer‐Hansen, S., Larsen, M., Mikkelsen, J. D., Møller, A. K. H., Mathé, A. A., & Wörtwein, G. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21027 · Cited by 36
The Wistar Kyoto Rat: A Model of Depression Traits
Redei, E. E., Udell, M. E., Woods, L. C. S., & Chen, H. (2022) · Current Neuropharmacology · doi:10.2174/1570159x21666221129120902 · Cited by 37
“…are either generated by nature, such as the WKY, or by selective breeding, e.g ., the WLI and WMI [156], the Flinders-sensitive line (FSL) rats [220], the selectively-bred high and low responders (bHR and bLR) [221], or the Roman high-and low-avoidance (RHA/Verh and RLA/Verh) [222], show some…”
Background
The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression
Thiele, S., Furlanetti, L. L., Pfeiffer, L.-M., Coenen, V. A., & Döbrössy, M. D. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.02.002 · Cited by 35
“FSL rats are a selectively bred rat strain mimicking several depressive-like symptoms such as reduced motivation, locomotion and exploration, altered sleep rhythms and weight loss, impaired spatial orientation and learning and memory deficits and altered neurotransmitter and hormone levels (Overstreet, 1993; Thiele et…”
Background
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test
West, C. H. K., & Weiss, J. M. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0048-x · Cited by 35
“This method uses the Flinder’s sensitive rat line, which Overstreet and colleagues have proposed as an animal model of depression (Overstreet 1986; Overstreet 1993).”
Method
The involvement of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) in blocking the therapeutic effect of electroconvulsive shocks in an animal model of depression
Maayan, R., Morad, O., Dorfman-Etrog, P., Overstreet, D. H., Weizman, A., & Yadid, G. (2005) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2004.10.005 · Cited by 35
“In addition, FSL rats display exaggerated immobility time in FST (Overstreet, 1993).”
Background
Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments
Hunt, R. H., & Tougas, G. H. (2002) · Best Practice & Research Clinical Gastroenterology · doi:10.1053/bega.2002.0356 · Cited by 34
Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression
Rummel, J., Voget, M., Hadar, R., Ewing, S. G., Sohr, R., Klein, J., Sartorius, A., Heinz, A., Mathé, A. A., Vollmayr, B., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.06.016 · Cited by 38
Dysregulation of the orexinergic system: A potential neuropeptide target in depression
Khairuddin, S., Aquili, L., Heng, B. C., Hoo, T. L. C., Wong, K.-H., & Lim, L. W. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.040 · Cited by 35
Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression
Cashman, J. R., Voelker, T., Johnson, R., & Janowsky, A. J. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.10.065 · Cited by 32
Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression
Wilhelm, C., Choi, D., Huckans, M. S., Manthe, L., & Loftis, J. M. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.11.001 · Cited by 33
“…to their cholinergic hypersensitivity, they express behavioral (e.g., reduced locomotor activity, increased immobility, and cognitive deficits (Overstreet, 1993)) and physiological (e.g., psychomotor retardation, lower body weight, and reduced appetite (Overstreet et al., 2005)) features…”
Background
Finding a biosignature for melancholic depression
Day, C. V., & Williams, L. M. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.72 · Cited by 32
Opposite behaviours in the forced swimming test are linked to differences in spatial working memory performances in the rat
Naudon, L., & Jay, T. M. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.009 · Cited by 32
Reconsidering depression as a risk factor for substance use disorder: Insights from rodent models
Rappeneau, V., & Bérod, A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.001 · Cited by 33
“…Line rats (FSL), derived from Sprague-Dawley rats and initially selectively bred for hypersensitivity to a cholinergic agent (Overstreet and Russell, 1982; Overstreet et al., 1979), subsequently displayed a range of behavioral and physiological alterations relevant to depression (Overstreet, 1993).”
Brain Mapping: The Applications
Mayberg, H. S., & McGinnis, S. M. (2000) · Elsevier eBooks · doi:10.1016/b978-012692545-6/50018-0 · Cited by 32
Suppression of reward-induced dopamine release in the nucleus accumbens in animal models of depression: Differential responses to drug treatment
Minami, S., Satoyoshi, H., Ide, S., Inoue, T., Yoshioka, M., & Minami, M. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.04.028 · Cited by 31

Authors: Overstreet, D. H.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Overstreet, David H.
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 1993-03
Volume: 17
Issue: 1
Pages: 51-68
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/s0149-7634(05)80230-1
OpenAlex: W1991527095
Cited by: 369
References: 170
Citations by year: 2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 5 · 2018: 10 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 8 · 2013: 18 · 2012: 9
FWCI: 2.77
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: Flinders Sensitive Line rats, animal models of depression, anhedonia, chronic mild stress, immobility, antidepressant efficacy, circadian rhythm, locomotor activity, REM sleep, face validity, construct validity, predictive validity
MeSH terms: Animals, Depression, Disease Models, Animal, Rats, Inbred Strains, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The flinders sensitive line rats: A genetic animal model of depression

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks