Brain 5-HT synthesis in the Flinders Sensitive Line rat model of depression: An autoradiographic study

Hasegawa, Shu; Nishi, Kyoko; Watanabe, Arata; Overstreet, David H.; Dikšić, Mirko

doi:10.1016/j.neuint.2005.11.012

Cited by 56 publications

(54 citation statements)

References 50 publications

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“…It should be noted that the levels of 5-HT and 5-HIAA were normalized following an 18 day treatment with a 5 mg/kg/day dose of desipramine. 36 FSL rats have lower 5-HT synthesis rates throughout the brain, relative to both FRL and SPD rats, 131 as measured using the α-[ [135][136][137] An increase in extracellular 5-HT levels produced by acute treatment with the selective 5-HT reuptake inhibitor (SSRI), citalopram, 138 resulted in a widespread decrease in 5-HT synthesis in FSL rats, while producing no change in SPD rats and an increase in 5-HT synthesis in FRL rats. 139 On the other hand, the effect of a chronic citalopram treatment on 5-HT synthesis in FSL rats was reversed from the acute effect, while having no effect on 5-HT synthesis in the FRL strain.…”

Section: Serotonergic Alterations In the Fsl Model Of Depressionmentioning

confidence: 94%

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Neurochemical and Behavioural Changes in Rat Models of Depression

Skelin¹,

Kovačević²,

Dikšić³

2011

Croat. Chem. Acta

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Abstract. Depression is one of the most prevalent psychiatric disorders with significant lifetime prevalence. The study of human depression is hindered by the relatively significant heterogeneity of this disorder. As a result of these heterogeneities, studies using a sound and representative animal model of depression are extremely valuable and, in general, provide important information regarding the neurochemical/biological changes occurring during depression and the subsequent treatment of its symptoms. In this review we concentrate on two solid rat models of depression: olfactory bulbectomized (OBX) rats and Flinders Sensitive Line (FSL) of rats. These two models were selected because they possess all three characteristics of a good animal model; face, predictive and constructive validities. We also emphasize the brain serotonergic system and we discuss the open field and forced swim test to assess behaviour. (doi: 10.5562/cca1817) Keywords: depression, olfactory bulbectomized rat model of depression, Flinders sensitive line rat, Flinders Resistant line rat, animal model of depression

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Section: Serotonergic Alterations In the Fsl Model Of Depressionmentioning

confidence: 94%

“…142 The high intra-neuronal levels of 5-HT may also account for the low 5-HT synthesis rates in the FSL rats. 131 The cerebral glucose utilization (CGU), an index of neuronal activity, 143 measured by […”

Section: Serotonergic Alterations In the Fsl Model Of Depressionmentioning

confidence: 99%

Neurochemical and Behavioural Changes in Rat Models of Depression

Skelin¹,

Kovačević²,

Dikšić³

2011

Croat. Chem. Acta

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“…The biological mechanisms leading to impaired autonomic control of the heart in depression are unknown. Disruption of 5-HT neurotransmission plays a major role in the etiology of depression: 5-HT levels (20) and 5-HT receptor levels, particularly 5-HT 1A receptors (30,34), in some areas of the brain are abnormal in depression.The Flinders-Sensitive Line (FSL) rat, bred for cholinergic hypersensitivity, is a well-validated genetic animal model of depression exhibiting a number of behavioral and neurochemical (11,47,48) similarities to depressed humans. Recently, we demonstrated reduced sBRS and HRV in anesthetized FSL rats compared with control strains (28), closely mimicking cardiovascular regulatory abnormalities in depressed humans.…”

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confidence: 99%

“…The Flinders-Sensitive Line (FSL) rat, bred for cholinergic hypersensitivity, is a well-validated genetic animal model of depression exhibiting a number of behavioral and neurochemical (11,47,48) similarities to depressed humans. Recently, we demonstrated reduced sBRS and HRV in anesthetized FSL rats compared with control strains (28), closely mimicking cardiovascular regulatory abnormalities in depressed humans.…”

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confidence: 99%

Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression

Hildreth¹,

Padley²,

Pilowsky³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Hildreth CM, Padley JR, Pilowsky PM, Goodchild AK. Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression. Am J Physiol Heart Circ Physiol 294: H474-H480, 2008. First published November 9, 2007 doi:10.1152/ajpheart.01009.2007.-Serotonin (5-HT) is crucial to normal reflex vagal modulation of heart rate (HR). Reduced baroreflex sensitivity [spontaneous baroreflex sensitivity (sBRS)] and HR variability (HRV) reflect impaired neural, particularly vagal, control of HR and are independently associated with depression. In conscious, telemetered Flinders-Sensitive Line (FSL) rats, a wellvalidated animal model of depression, we tested the hypothesis that cardiovascular regulatory abnormalities are present and associated with deficient serotonergic control of reflex cardiovagal function. In FSL rats and control Flinders-Resistant (FRL) and Sprague-Dawley (SD) rat strains, diurnal measurements of HR, arterial pressure (AP), activity, sBRS, and HRV were made. All strains had normal and similar diurnal variations in HR, AP, and activity. In FRL rats, HR was elevated, contributing to the reduced HRV and sBRS in this strain. In FSL rats, sBRS and high-frequency power HRV were reduced during the night, indicating reduced reflex cardiovagal activity. The ratio of low-to high-frequency bands of HRV was increased in FSL rats, suggesting a relative predominance of cardiac sympathetic and/or reflex activity compared with FRL and SD rats. These data show that conscious FSL rats have cardiovascular regulatory abnormalities similar to depressed humans. Acute changes in HR, AP, temperature, and sBRS in response to 8-hydroxy-2-(di-npropylamino)tetralin, a 5-HT 1A, 5-HT1B, and 5-HT7 receptor agonist, were also determined. In FSL rats, despite inducing an exaggerated hypothermic effect, 8-hydroxy-2-(di-n-propylamino)tetralin did not decrease HR and AP or improve sBRS, suggesting impaired serotonergic neural control of cardiovagal activity. These data suggest that impaired serotonergic control of cardiac reflex function could be one mechanism linking reduced sBRS to increased cardiac risk in depression.serotonin-1A receptors; 8-hydroxy-2-(di-n-propylamino)tetralin; Flinders Sensitive Line rat; vagus; telemetry TONIC AND REFLEX CONTROL of heart rate (HR) is dependent on the balance of parasympathetic (vagal) and sympathetic neural input. Disruption of this balance, through a decrease in vagal tone or an increase in sympathetic tone, leads to cardiac dysfunction and/or arrhythmias (35,43).Tonic levels of cardiovagal activity and, consequently, the level of resting HR are controlled by the activity of cardiac vagal preganglionic neurons (CVPN) located in the nucleus ambiguus (NA) and dorsal motonucleus of the vagus (44). Within the NA, the rhythmic activity of CVPN is dependent on excitatory and inhibitory synaptic inputs (22, 44), including ongoing baroreflex [mediated via the nucleus of the solitary tract (NTS)] and respiratory input (9, 33). Phasic inhibition of inhibitory...

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“…The FSL exhibit many biochemical abnormalities; alteration in 5-HT levels and synthesis [24,70], different 5-HT receptor densities [45,64], differences in response of the 5-HT system to antidepressant treatments [30,31,36,46], increased regional blood glucose utilization [29], and changes in dopaminergic [18,22] and glutaminergic [42] neurotransmission. mGluR3 have been implicated in the control of the Brain-Derived Neurotrophic Factor (BDNF) production, which is lower in the FSL rats [67] and well established in the pathophysiology of depression [6].…”

Section: Introductionmentioning

confidence: 99%

Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: An autoradiographic study

Kovačević

Skelin

Minuzzi

et al. 2012

Brain Research Bulletin

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Depression is a brain disorder and there is still only a partial understanding of its underlying pathophysiology. Antidepressant medications with a fast onset have not yet been developed. In addition to the monoaminergic systems, the brain glutaminergic system has been implicated in the etiology of depression. Animal studies of depression have gained importance because they permit a more invasive manipulation of the subjects than human studies. In the present study, we measured the densities of the brain regional metabotropic glutaminergic receptor 5 (mGluR5) in the Flinders Sensitive Line (FSL) rat model of depression and two groups of control rats, the Flinders Resistant Line (FRL) and Sprague Dawley (SPD), the parent strain for both the FSL and FRL rats. The FSL rats showed lower densities of mGluR5 in many brain regions compared to either the SPD and/or FRL rats. In addition, the densities in the FRL rats were larger than in the SPD rats, suggesting possible problems in using FRL rats as controls. The presented data suggest that mGluR5 is lower in animal models of depression which could be related to the cognitive and emotional dysfunctions in the FSL rat model of depression and could be relevant to a better understanding of depression in humans. Keywords

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Brain 5-HT synthesis in the Flinders Sensitive Line rat model of depression: An autoradiographic study

Cited by 56 publications

References 50 publications

Neurochemical and Behavioural Changes in Rat Models of Depression

Neurochemical and Behavioural Changes in Rat Models of Depression

Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression

Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: An autoradiographic study

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