Animal models of depression: olfactory lesions affect amygdala, subventricular zone, and aggression

Mucignat‐Caretta, Carla; Bondı̀, Michela; Caretta, Antonio

doi:10.1016/j.nbd.2004.03.007

Cited by 41 publications

(30 citation statements)

References 59 publications

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“…The olfactory bulbs send direct connections to the cortex (pyriform, entorhinal, and parahippocampal), amygdala and BNST (Haberly and Price, 1977;Leonard and Tuite, 1981). Many of the behavioral alterations observed in the OB rat have been attributed to severed connections between the olfactory organs and various brain centers, with much emphasis being placed on the resultant disinhibition of the amygdala following removal of the bulbs (Leonard and Tuite, 1981;Van Riezen and Leonard, 1990;McNish and Davis, 1997;Mucignat-Caretta et al, 2004). Increased neuronal activation in the CeAMY and BLA of the OB rat following open-field exposure confirms that the amygdaloid nuclei are integral in mounting a stress response in these animals.…”

Section: Discussionmentioning

confidence: 99%

Chronic Fluoxetine Treatment Attenuates Stressor-Induced Changes in Temperature, Heart Rate, and Neuronal Activation in the Olfactory Bulbectomized Rat

Roche

Harkin

Kelly

2006

Neuropsychopharmacol

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The olfactory bulbectomized (OB) rat is a well-characterized animal model that exhibits a number of behavioral and neurochemical changes that have relevance to clinical depression. Hyperactivity in the open field is the most widely used parameter assessed in this model and is reversed following chronic, but not acute, antidepressant treatment. This study investigated OB-induced alterations in heart rate, body temperature, and neuronal activation following open-field exposure and the impact of chronic treatment with fluoxetine on these parameters. Upon placement in the open field, OB rats exhibited a characteristic hyperactivity response. Heart rate and body temperature were increased in sham-operated rats following open-field exposure, a predictable response to stress, which was significantly reduced in OB rats. Moreover bulbectomy reduced open field-induced cFOS expression in the basal nucleus of the stria terminalis while concurrently increasing expression in the hippocampus, amygdala, paraventricular nucleus of the thalamus, and dorsal raphe nucleus. Chronic fluoxetine treatment (10 mg/kg subcutaneous once daily for 5 weeks) attenuated all of these OB-associated changes. In conclusion, OB rats exhibit alterations in behavior, body temperature, heart rate, and neuronal activation in response to open-field exposure, which are reversed following chronic fluoxetine administration. These results identify stress-sensitive regions within the brain which are altered following bulbectomy and which may underlie the abnormal behavioral and physiological changes observed in this rodent model of depression.

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Section: Discussionmentioning

confidence: 99%

Chronic Fluoxetine Treatment Attenuates Stressor-Induced Changes in Temperature, Heart Rate, and Neuronal Activation in the Olfactory Bulbectomized Rat

Roche

Harkin

Kelly

2006

Neuropsychopharmacol

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“…This test was performed on day 1 to evaluate locomotor and exploratory activities, and emotional reactivity to a novel environment [26]. Mice were individually moved to a plastic cage (55×33×20 cm), with opaque walls and black floor, and video-recorded for 3 min.…”

Section: Methodsmentioning

confidence: 99%

Effects of a Copper-Deficient Diet on the Biochemistry, Neural Morphology and Behavior of Aged Mice

et al. 2012

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Copper dyshomeostasis has been suggested as an aetiological risk factor for some neurodegenerative diseases, such as Alzheimer’s disease. However, the precise mechanism at the base of this involvement is still obscure. In this work, we show the effects of a copper-deficient diet in aged CD1 mice and the influence of such a diet on: a) the concentration of various metal ions (aluminium, copper, iron, calcium, zinc) in the main organs and in different brain areas; b) the alteration of metallothioneins I-II and tyrosine hydroxylase immunopositivity in the brain; c) behavioural tests (open field, pole, predatory aggression, and habituation/dishabituation smell tests). Our data suggested that the copper-deficiency was able to produce a sort of “domino effect” which altered the concentration of the other tested metal ions in the main organs as well as in the brain, without, however, significantly affecting the animal behaviour.

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“…Thus, for the functional validation of some transcripts identified as possible drug targets, further studies will be necessary to assess the effect of transcriptional regulation in one or more rodent models of depression. [38][39][40][41][42][43] Another apparent limitation is that transcriptional profiles for the different treatments were compared only at the time points corresponding to clinical efficacy, which differed for each treatment being 2 days for ECT, 1 day for SD and 14 days for FLX. Thus, a comparative analysis of transcriptional changes induced at the same time points for all treatments is missing.…”

Section: Number Of Transcripts Affected By Single and Multiple Treatmmentioning

confidence: 99%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.

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Animal models of depression: olfactory lesions affect amygdala, subventricular zone, and aggression

Cited by 41 publications

References 59 publications

Chronic Fluoxetine Treatment Attenuates Stressor-Induced Changes in Temperature, Heart Rate, and Neuronal Activation in the Olfactory Bulbectomized Rat

Chronic Fluoxetine Treatment Attenuates Stressor-Induced Changes in Temperature, Heart Rate, and Neuronal Activation in the Olfactory Bulbectomized Rat

Effects of a Copper-Deficient Diet on the Biochemistry, Neural Morphology and Behavior of Aged Mice

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

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