Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoaminergic neurotransmission is a key element in the physiopathology of depressive disorders, but information is still sparse on animal models of this disease. Here, we used the olfactory bulbectomy (OBX) model of depression to characterize cAMP-second messenger signaling pathways, i.e., adenylyl cyclase activity (basal, sodium fluoride (NaF)- and forskolin-stimulated conditions) as well as Gi and Gs protein levels in different regions of the limbic system. Two weeks after surgery and compared to sham controls, OBX rats displayed reduced NaF-stimulated adenylyl cyclase activity and increased Gi/Gs ratios in the hypothalamus, pre-frontal and cingulate cortices but not in the amygdala, hippocampus and caudate nucleus. No differences were found in basal or forskolin-stimulated conditions. The observed reduction of adenylyl cyclase activity induced by NaF and the increase in the Gi/Gs ratio could explain the changes in neurotransmission in OBX rats as well as in humans with depression.
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PMID:Effect of olfactory bulbectomy on adenylyl cyclase activity in the limbic system. 1913 18

Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB(1) receptor density ([(3)H]CP55490 binding) and functionality (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB(1)-receptor signaling in PFC observed following OBX. The CB agonist Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Delta(9)-tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB(1) receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.
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PMID:Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine. 1918 63

Since long-term treatment with imipramine increases the neuropeptide Y (NPY) levels in the frontal cortex and hypothalamus, the possibility exists that the antidepressant action of imipramine may be mediated via the NPY Y1 receptors. Bilateral olfactory bulbectomy (OBX) resulted in hyperactivity (increased number of ambulation, rearing and grooming episodes) in open field test (OFT) suggesting a depression-like condition. Chronic (14 days) administration of NPY, NPY Y1/Y5 receptor agonist [Leu(31), Pro(34)]-NPY (intracerebroventricular, i.c.v.) or tricyclic antidepressant imipramine (intraperitoneal) to OBX rats dose-dependently resulted in decreased hyperactivity in OFT, while selective NPY Y1 receptor antagonist BIBP3226 (i.c.v.) produced opposite effects. The antidepressant actions of imipramine were enhanced by co-administration of NPY or [Leu(31), Pro(34)]-NPY, and antagonized by BIBP3226 given at sub-effective doses. The data suggest that NPY, acting via NPY Y1 receptors, may be involved in antidepressant action of imipramine in OBX rats.
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PMID:Neuropeptide Y modulates the antidepressant activity of imipramine in olfactory bulbectomized rats: involvement of NPY Y1 receptors. 1925 1

1-(m-Chlorophenyl)piperazine (mCPP) has a fairly complex neuropsychopharmacological profile owing to its affinity to multiple serotonergic receptors. This investigation was designed to establish the effect of mCPP on rodent depression-like behaviour. mCPP was screened in a rodent behavioural test battery comprising of validated antidepressant assays and interaction studies with conventional antidepressants and ligands were carried out in forced swim and tail suspension test (in mice). mCPP (1 mg/kg, i.p.) exhibited depressant-like effects in forced swim and tail suspension test (in mice), without influencing the locomotor status. Potentiation of 5-hydroxytryptophan/pargyline induced head twitches (in mice) and hyperthermic effects (in rats) were observed at the same dose level. Further, the behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic mCPP (1-2 mg/kg) treatment as observed from the modified open field, elevated plus maze and social interaction paradigms. Interaction studies revealed that the mCPP induced depressant-like effects were reversed by ketanserin, escitalopram, amitriptyline, ziprasidone, venlafaxine pretreatments but not by bupropion, harmane, ondansetron, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and MK-801. In conclusion, this study provided ample evidence that the stimulation of 5-HT(2A) receptors underlies the depressogenic-like effect of mCPP. Finally, the mCPP induced depression-like behaviour in rodents is envisaged as a modified antidepressant assay to identify novel serotonergic antidepressants.
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PMID:1-(m-Chlorophenyl)piperazine induces depressogenic-like behaviour in rodents by stimulating the neuronal 5-HT(2A) receptors: proposal of a modified rodent antidepressant assay. 1926 87

The effects of VIP microinjected unilaterally (left or right) into the hippocampal CA1 area at a dose of 10 and 100 ng or bilaterally (10 ng), on nociception of male Wistar rats with a model of depression (bilateral olfactory bulbectomy-OBX) were studied. Nociception was examined applying mechanical pressure on the left hind paw of the rat (analgesy-meter test). It was found that in OBX rats the pain threshold is increased. VIP showed differential effects depending on the side and dose of administration. The pain threshold after left-side microinjections of VIP into the hippocampal CA1 area of OBX rats was significantly higher than that after injections into right-side. There are no significant differences between right-side VIP-treated and OBX rats. Bilateral microinjections of VIP also exerted antinociceptive effect. These findings suggest that the hippocampal lateralized antinociceptive effect of VIP in OBX rats depends on the hemisphere of injection and suggest that VIP-ergic neurons in the hippocampal CA1 area may play differential role in nociception of rats with a model of depression.
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PMID:Differential involvement of hippocampal vasoactive intestinal peptide in nociception of rats with a model of depression. 1946 83

Treatment with pramipexole, a dopamine D(3)/D(2) receptor agonist, reduces depressive symptoms in patients suffering from Parkinson's disease. To test the putative antidepressant quality of pramipexole, its effects were assessed in one of the most attractive animal models of depression, the olfactory bulbectomized (OBX) rat. Two experiments studied the effects of pramipexole on bulbectomy-induced hyperactivity. In experiment I, pramipexole was tested at 0.3 and 1.0 mg/kg together with the reference dopamine D(3) receptor agonist 7-OH-DPAT (0.1 mg/kg) and the tri-cyclic antidepressant imipramine (10 mg/kg). In experiment II, pramipexole was tested at lower doses: 0.03 and 0.1 mg/kg, with the same reference compounds. All animals were tested in the open field on days one (acute), seven (sub-chronic) and fourteen (chronic) of administration, as well as one week after cessation of treatment. Pramipexole, in a U-shaped dose response, reduced bulbectomy-induced hyperactivity after (sub) chronic but not acute administration (like imipramine and 7-OH-DPAT). The highest dose of pramipexole (1.0 mg/kg) did not reduce OBX hyperactivity during treatment. However, one week after cessation of treatment, all pramipexole (including the 1.0 mg/kg dose), 7-OH-DPAT and imipramine groups showed a reduction in OBX-induced hyperactivity. Pramipexole and 7-OH-DPAT exert an antidepressant profile in the OBX-rat model in normalizing bulbectomy-induced hyperactivity during (sub) chronic treatment. Moreover, treatment with both these compounds induced long-lasting changes in the bulbectomized brain similar to established antidepressants, strongly predicting antidepressant activity in major depression.
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PMID:Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats. 1954 14

We evaluated the effects of nicotine on cell and oxidative damage caused by olfactory bulbectomy (OBX). The rats were divided into seven groups as follows: i) control; ii) vehicle (6% ethanol); iii) treated with nicotine; iv) sham operated; v) olfactory bulbectomy (OBX); vi) OBX+vehicle; and vii) OBX+Nic. The OBX was performed using the trepanation of frontal bone. The olfactory bulbs were cut and removed without damage to the frontal cortex. Two weeks after surgery nicotine was administered chronically once daily for 14 days, intraperitoneally (i.p.) in doses of 1.5 mg/kg, two weeks after surgery. OBX caused an increase in lipid peroxidation products and caspase-3 but prompted a reduction in reduced glutathione (GSH) content and antioxidative enzyme activity. All these changes were reverted by treatment of nicotine (14 days). In conclusions: i) OBX induces oxidative stress and cell death by apoptosis; and ii) nicotine presents antidepressant and antioxidant effect. All these findings suggest that nicotine would be a therapeutic tool for depression, although more studies are needed in this area to define the appropriate treatment regime.
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PMID:Protective effect of nicotine on oxidative and cell damage in rats with depression induced by olfactory bulbectomy. 1988 66

The olfactory bulbectomized (OBX) rat is an animal model of depression with neurochemical, neuroendocrinological and behavioral features resembling some human depression. d-Fenfluramine is a 5-HT releasing drug, frequently used in the study of the responsivity of the 5-HT system in subjects with psychiatric disorders, including depression. The aim of the study is to assess the influence of the serotonin-releaser, d-fenfluramine, in the OBX rat model of depression, as measured by the change in the regional cerebral glucose utilization rCGU) following d-fenfluramine injection. Male Sprague-Dawley rats (160-180 g) were used. The rats were divided into OBX and Sham groups. Two weeks following the olfactory bulbectomy or the sham surgery, six rats (randomly assigned) from each group received an i.p. injection of d-fenfluramine with a dose of 5 mg/kg or the same volume of saline. Twenty minutes later, the rCGU rates were measured using 2-[(14)C]deoxyglucose autoradiography. The general linear model statistical analysis has shown that the rCGU in the sham-operated rats treated with d-fenfluramine, compared to the sham-operated rats treated with saline, was lower in 14 (36%) out of 39 examined brain regions. There was no significant difference in the rCGU between the OBX rats treated with d-fenfluramine and OBX rats treated with saline. The results suggest the blunted capacity of the 5-HT system in OBX rats to respond to the challenge by the 5-HT releasing compound, d-fenfluramine. This resembles similar findings in clinical studies on depressed patients.
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PMID:Acute challenge with d-fenfluramine decreases regional cerebral glucose utilization in Sham, but not in OBX, rats: an autoradiographic study. 1991 94

Bilateral olfactory bulbectomy (OBX) in rodents produces behavioral and neurochemical changes associated clinically with depression and schizophrenia. Most notably, OBX induces hyperlocomotion in response to the stress of exposure to a novel environment. We examined the role of the endocannabinoid system in regulating this locomotor response in OBX and sham-operated rats. In our study, OBX-induced hyperactivity was restricted to the first 3 min of the open field test, demonstrating the presence of novelty (0-3 min) and habituation (3-30 min) phases of the open field locomotor response. Levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide were decreased in the ventral striatum, a brain region deafferented by OBX, whereas cannabinoid receptor densities were unaltered. In sham-operated rats, 2-AG levels in the ventral striatum were negatively correlated with distance traveled during the novelty phase. Thus, low levels of 2-AG are reflected in a hyperactive open field response. This correlation was not observed in OBX rats. Conversely, 2-AG levels in endocannabinoid-compromised OBX rats correlated with distance traveled during the habituation phase. In OBX rats, pharmacological blockade of cannabinoid CB(1) receptors with either AM251 (1 mg kg(-1) i.p.) or rimonabant (1 mg kg(-1) i.p.) increased distance traveled during the habituation phase. Thus, blockade of endocannabinoid signaling impairs habituation of the hyperlocomotor response in OBX, but not sham-operated, rats. By contrast, in sham-operated rats, effects of CB(1) antagonism were restricted to the novelty phase. These findings suggest that dysregulation in the endocannabinoid system, and 2-AG in particular, is implicated in the hyperactive locomotor response induced by OBX. Our studies suggest that drugs that enhance 2-AG signaling, such as 2-AG degradation inhibitors, might be useful in human brain disorders modeled by OBX.
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PMID:A role for 2-arachidonoylglycerol and endocannabinoid signaling in the locomotor response to novelty induced by olfactory bulbectomy. 2004 5

The first line of antidepressant treatment nowadays are selective serotonin reuptake inhibitors. Although they are relatively safe to use, selective serotonin reuptake inhibitors (SSRIs) can induce severe side effects. New promising antidepressants may be the triple monoamine reuptake inhibitors, which not only enhance serotonin and norepinephrine neurotransmission, but also increase brain dopamine levels. Recently it has been shown that one of the triple reuptake inhibitors, DOV 216,303 has antidepressant-like effects in the olfactory bulbectomy (OBX) model of depression, but the alterations in monoaminergic neurotransmission in these animals are still unknown. In the present study we investigated not only the effect of acute, but also chronic treatment of DOV 216,303 in OBX rats on monoamine and metabolite levels. The main results are decreased baseline dopamine levels in the prefrontal cortex one day after OBX, while 38days after OBX no difference could be observed in monoamine levels after vehicle treatment. Treatment with DOV 216,303 leads to increased extracellular levels of serotonin and norepinephrine neurotransmission, but also increased dopamine levels in OBX animals as well as their controls. This increase could be observed after one single administration, but also after chronic treatment. However, a DOV 216,303 challenge in chronically treated animals resulted in lower monoamine concentrations than the same challenge in untreated animals. More research is needed to investigate this seemingly hyporesponsivity to chronic DOV 216,303 treatment.
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PMID:The putative antidepressant DOV 216,303, a triple reuptake inhibitor, increases monoamine release in the prefrontal cortex of olfactory bulbectomized rats. 2015 45


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