0000000000405092
AUTHOR
Eberhard Fuchs
Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat
Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-re…
Development of the first marmoset-specific DNA microarray (EUMAMA): a new genetic tool for large-scale expression profiling in a non-human primate
Abstract Background The common marmoset monkey (Callithrix jacchus), a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. In contrast to the growing interest for the marmoset as an animal model, the molecular tools for genetic analysis are extremely limited. Results Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA) containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of …
Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment.
Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferatio…
The Chronic Psychosocial Stress Paradigm in Male Tree Shrews: Evaluation of a Novel Animal Model for Depressive Disorders
To improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews, which is based on the territorial behaviour of these animals that can be used to establish naturally occurring challenging situations under experimental control in the laboratory. Co-existence of two males in visual and olfactory contact leads to a stable dominant-subordinate relationship, with subordinates showing distinct stress-induced behavioural and neuroendocrine alterations that are comparable to the symptoms observed during episodes of depress…
Anterograde tracing of retinal afferents to the tree shrew hypothalamus and raphe
The anterograde neuronal transport of Cholera toxin B subunit (CTB) was used in this study to label the termination of retinal afferents in the hypothalamus of the tree shrew Tupaia belangeri. Upon pressure-injection of the substance into the vitreous body of one eye, a major projection of the retinohypothalamic tract (RHT) was found to the hypothalamic suprachiasmatic nuclei (SCN). Although the innervation pattern was bilateral, the ipsilateral SCN received a somewhat stronger projection. Labeling was also found in the supraoptic nucleus and its perinuclear zone, respectively, mainly ipsilaterally as well as in the bilateral para- and periventricular hypothalamic regions without lateral pr…
Effects of escitalopram on the regulation of brain-derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress.
Escitalopram (ES-CIT) is a widely used, highly specific antidepressant. Until now there has been very little evidence on how this drug under pathological conditions affects an important feature within the pathophysiology of stress-related disorders such as depression: the endogenous neurotrophins. By using a well-characterized rat model in which chronic stress induces depressive-like behavior, the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in representative brain regions and serum using a highly sensitive improved fluorometric two-site ELISA system. There was a significant increase of BDNF in the left and right cortices aft…
Day- and night-time contents of monoamines and their metabolites in the medial preoptic area of the rat hypothalamus.
The present study was conducted to investigate whether monoamines and their metabolites in the medial preoptic area (mPOA) of the rat hypothalamus exhibit differences in their contents between day and night. We therefore sampled the mPOA from adult animals of either sex at the middle of the light or dark period, respectively, and analyzed the tissue by means of high performance liquid chromatography with electrochemical detection. We found that, in female animals at mid-night, dopamine and 3,4-dihydroxyphenyl acetic acid (DOPAC) was reduced to 43 and 30%, respectively, of daytime levels, while the norepinephrine content was doubled. No significant differences were observed in male animals. …
Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment.
Analysis of post-mortem tissue from patients with affective disorders has revealed a decreased number of glial cells in several brain areas. Here, we examined whether long-term psychosocial stress influences the number and morphology of hippocampal astrocytes in an animal model with high validity for research on the pathophysiology of major depression. Adult male tree shrews were submitted to 5 weeks of psychosocial stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number and somal volume of glial fibrillary acidic protein-positive astrocytes in the hippocampal formation. Stress significantly decreased both the number (-25%) and…
Diurnal variation of corticotropin-releasing factor binding sites in the rat brain and pituitary.
1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal (HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF system are subject to diurnal variations. 2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala, bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus, hippocampus, and locus ceruleus of rats by in vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also es…
Effects of fluoxetine on behavioral deficits evoked by chronic social stress in rats.
Recently, we described an advanced model of chronic social stress in male rats based on the resident intruder paradigm. In this model, rats subjected to daily social stress for 5 weeks showed behavioral changes resembling anhedonia and motivational deficits in humans. In the present study, male Wistar rats were subjected to 5 weeks of daily social defeat by an aggressive conspecific and concomitant treatment with the antidepressant drug fluoxetine (10 mg/kg) after the first week of stress. Compared with controls, rats exposed to chronic stress had significantly reduced locomotor and exploratory activity (rearing and sniffing) and diminished preference for sucrose solution. These effects wer…
Diazepam has no beneficial effects on stress-induced behavioural and endocrine changes in male tree shrews.
Abstract VAN KAMPEN, M., U. SCHMITT, C. HIEMKE AND E. FUCHS. Diazepam has no beneficial effects on stress-induced behavioural and endocrine changes in male tree shrews. PHARMACOL BIOCHEM BEHAV 65 (3) 539–546, 2000.—The present study evaluated the effect of subchronic oral treatment of psychosocially stressed male tree shrews with diazepam on locomotor activity, marking behavior, avoidance behavior, and urinary cortisol and noradrenaline. To mimic a realistic situation of anxiolytic intervention, the treatment started 14 days after the beginning of psychosocial stress; at that time, the stress-induced behavioral and endocrine alterations had been established. The drug (5 mg/kg/day) was admin…
Chronic psychosocial stress and antidepressant treatment in tree shrews: time-dependent behavioral and endocrine effects.
Abstract Social defeat has been shown to cause a number of behavioral, physiological, and central nervous changes in male tree shrews. The present study was designed to assess: (i) a potential time lag in the occurrence of behavioral alterations (locomotor activity, self-grooming, marking behavior, food and water intake, and avoidance behavior) after stress and long-term antidepressant treatment; and (ii) to investigate potential interactions between behavioral and endocrine variables (urinary cortisol and norepinephrine). Male tree shrews were submitted to chronic psychosocial stress for 39 days. In this paradigm, the stress-induced behavioral and endocrine alterations in subordinate anima…