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)

GABAergic mechanisms have been implicated in the bilateral olfactory bulbectomy (OBX) animal model of depression, where GABAB receptor binding sites have been shown to decrease markedly at specific time points after OBX. However, as no detailed time course of events has been determined, the present study investigated the effects of OBX on high-affinity GABAA, GABAB, beta-adrenergic, and benzodiazepine receptor binding parameters in membrane preparations from rat brain regions at weekly intervals (1-4 weeks) after OBX. Persistent significant increases (40-60%) in Bmax values of high affinity GABAA receptors were observed in the frontal cortex throughout the period investigated following OBX. Bmax values in the hippocampus increased significantly after 1 week (53%) but were not statistically significant thereafter. No changes in GABAA binding parameters were observed in the hypothalamus or cerebellum. Conversely, GABAB receptor densities were significantly decreased in the frontal cortex after 1 (-38%) and 2 (-41%) weeks and moderately decreased 3 and 4 weeks (-27 and -23%, respectively) after OBX, while in the cerebellum they were significantly increased after 1 week (96%) and returned to sham-operated levels by 3 weeks. No changes in GABAB receptor binding parameters were observed in the hippocampus or hypothalamus. Binding parameters for benzodiazepine receptor binding sites or beta-adrenoceptors were not modified throughout the time course. GABAergic transmission, reflected by changes in GABAA and GABAB receptor density in the frontal cortex, may be altered in OBX rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of olfactory bulbectomy on GABAA and GABAB receptors in the rat brain. 790 86

Geriatric depression exhibits biological and therapeutic differences relative to early-onset depression. We studied olfactory bulbectomy (OBX), a paradigm that shares major features of human depression, in young versus aged rats to determine mechanisms underlying these differences. Young OBX rats showed locomotor hyperactivity and a loss of passive avoidance and tactile startle. In contrast, aged OBX animals maintained avoidance and startle responses but showed greater locomotor stimulation; the aged group also exhibited decreased grooming and suppressed feeding with novel presentation of chocolate milk, effects which were not seen in young OBX. These behavioral contrasts were accompanied by greater atrophy of the frontal/parietal cortex and midbrain in aged OBX. Serotonin transporter sites were increased in the cortex and hippocampus of young OBX rats, but were decreased in the aged OBX group. Cell signaling cascades also showed age-dependent effects, with increased adenylyl cyclase responses to monoaminergic stimulation in young OBX but no change or a decrease in aged OBX. These data indicate that there are biological distinctions in effects of OBX in young and aged animals, which, if present in geriatric depression, provide a mechanistic basis for differences in biological markers and drug responses. OBX may provide a useful animal model with which to test therapeutic interventions for geriatric depression.
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PMID:Modeling geriatric depression in animals: biochemical and behavioral effects of olfactory bulbectomy in young versus aged rats. 1008 22

The effects of bilateral olfactory bulbectomy (OBX) on prepro-enkephalin, thyrotropin-releasing hormone, and D-2 receptor mRNA levels in the ventral striatum were examined by in situ hybridization histochemistry. Pre- pro-enkephalin mRNA levels were significantly increased in the olfactory tubercle (OT), but not in the nucleus accumbens, 14 days following bilateral OBX. Levels of D-2 receptor mRNA were also increased in the OT, though to a lesser degree. Prepro-thyrotropin-releasing hormone mRNA was unaffected by OBX. A separate experiment revealed no effect of OBX on enkephalin gene expression 7 days following surgery but a comparable elevation in pre- pro-enkephalin mRNA 14 and 28 days post-surgery. The findings are consistent with previously-reported effects of dopamine lesions on striatal gene expression, suggesting that the observed effects may be mediated by deafferentation-induced alterations in dopaminergic transmission in the OT. Altered dopaminergic function in the OT may be particularly relevant to the 'anhedonia' that has been associated with the olfactory bulbectomized rat model of depression.
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PMID:Olfactory bulbectomy increases prepro-enkephalin mRNA levels in the ventral striatum in rats. 1065 93

Olfactory bulbectomized (OBX) rats show a variety of behavioral and biochemical deficits that parallel human depression. We investigated the expression of glutamate receptor subtypes in cortical and subcortical brain regions following bilateral olfactory bulbectomy in adult rats. Quantitative receptor autoradiography using [(125)I]MK-801 (NMDA receptor), [(3)H]AMPA (AMPA receptor), and [(3)H]kainate (kainate receptor) was performed on brain sections at 1-5 weeks following olfactory bulbectomy. Our results show an elevation of NMDA receptors in the medial prefrontal cortex within 1 week following bulbectomy, which persisted up to at least 5 weeks post-bulbectomy. Neither kainate nor AMPA receptors were altered in any brain region examined. The potential significance of these results is discussed in light of experimental findings supporting a role for NMDA receptors in the mechanism of action of antidepressant drugs and the pathophysiology of major depression.
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PMID:Olfactory bulbectomy alters NMDA receptor levels in the rat prefrontal cortex. 1088 Oct 36

Geriatric depression is often associated dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, and with poor responsiveness to antidepressants that work through inhibition of monoamine reuptake; accordingly, it has been suggested that MAO inhibitors may represent a therapeutic alternative in this group. In the current study, we evaluated expression of MAO subtypes in brain regions of young and aged rats subjected to olfactory bulbectomy (OBX), a procedure that reproduces many of the biochemical and functional changes associated with human depression. Activities of both MAO A and B were elevated in aged rats as compared to young rats in most regions, but not in the midbrain, and the OBX lesion failed to produce any change in this pattern. These results stand in contrast to the differential effects of glucocorticoids, which reduce brain MAO in young animals but induce activity in aged rats. Our results support the view that the aged brain possesses biochemical characteristics that distinguish its monoamine biochemistry from that of young brain, and that these distinctions may work in conjunction with HPA axis dysregulation to influence the etiology and therapy of geriatric depression. The use of appropriate animal models for depression and for disruption of HPA axis function can allow for the testing of potential human biomarkers (such as platelet MAO) that may serve to predict treatment outcome.
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PMID:Regional differences in brain monoamine oxidase subtypes in an animal model of geriatric depression: effects of olfactory bulbectomy in young versus aged rats. 1105 94

Major depressive disorder (MDD) affects women to a greater extent then men; however, the few studies that have examined the role of gender in an animal model of depression have shown inconsistent results. The purpose of the present study was to determine if the gonadal hormone milieu of the animal modulated behavioral changes following olfactory bulbectomy (OBX), a well-documented animal model of depression. Body weight, sucrose preference levels and open-field activity levels were measured once a week for a period of 2 weeks in gonadally intact and gonadectomized male and female rats. Following these baseline measurements, animals underwent either OBX or sham surgery. Body weight, sucrose preference and activity levels were assessed for 4 weeks post-OBX surgery. OBX-gonadectomized animals exhibited higher activity levels than OBX gonadally intact and control animals. This effect of gonadectomy was more robust in males. OBX-females (both intact and gonadectomized) exhibited significantly lower sucrose preference levels than OBX-males (both intact and gonadectomized) and control animals. These results suggest that the gonadal hormone milieu of the animal plays a role in modulating sucrose preference and activity levels following OBX.
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PMID:Gender and gonadal hormone effects in the olfactory bulbectomy animal model of depression. 1111 99

Bilateral olfactory bulbectomy (OBX) in rats produces a well-characterized syndrome of behavioral, physiological, and neurochemical changes identical to those seen in depression. Previous experiments using in situ hybridization histochemistry have demonstrated that OBX increases prepro-neuropeptide-Y (NPY) and prepro-enkephalin (ENK) mRNA levels in limbic structures. The present experiments determined whether increases in peptide immunoreactivity occur in conjunction with increases in mRNA levels following OBX. In situ hybridization analyses in olfactory bulbectomized and sham-operated rats revealed increased prepro-ENK mRNA in the piriform cortex (PIR) and olfactory tubercles (OTs) of bulbectomized rats. Prepro-NPY mRNA levels were significantly increased in the PIR of bulbectomized rats as comapred to controls. Radioimmunoassays (RIAs) revealed significant elevations in ENK-like immunoreactivity in the OTs following OBX. NPY-like immunoreactivity was significantly elevated in the PIR following OBX. These data reveal that OBX-induced increases in ENK-like immunoreactivity occur concomitantly with increases in prepro-ENK mRNA, and NPY-like immunoreactivity occur concomitantly with increases in prepro-NPY mRNA.
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PMID:Olfactory bulbectomy increases met-enkephalin- and neuropeptide-Y-like immunoreactivity in rat limbic structures. 1112 98

Rat bilateral olfactory bulbectomy (OBX) serves as a useful model in the study of depression and the mechanisms of action of antidepressant treatments. Considering the evidence of NMDA receptors involvement in depression, the present study was undertaken in order to investigate the time-course effects of OBX on the NMDA receptor function. Following bilateral olfactory bulbectomy, rats display an increase in locomotor activity and changes in other types of behavior in a novel environment. Autoradiographic experiments using the noncompetitive NMDA antagonist [(125)I]-iodo-MK-801 as the labeling agent showed that this increase in behavioral activities corresponds to a decrease in [(125)I]-iodo-MK-801 binding in a number of brain regions. In most regions, this reduction reached significance by the third week following OBX. However, in some cortical areas-a nucleus of the thalamus (AV) and one of the amygdala (LA)-this reduction was already significant in the first or second week following OBX and lasted throughout the 4 weeks of the study. We also compared the behavioral modifications induced by a challenge injection of MK-801 (0.2 mg/kg i.p.) in OBX and sham-operated rats. This challenge is known to induce hyperlocomotion and a number of stereotypies in naive rats. These effects were drastically reduced in OBX as compared to sham-operated rats. These data are consistent with the above-mentioned decrease in cerebral binding of MK-801 to NMDA receptors.
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PMID:Effects of bilateral olfactory bulbectomy on N-methyl-D-aspartate receptor function: autoradiographic and behavioral studies in the rat. 1157 46

Sigma (sigma) ligands have been shown to modulate NMDA receptor activity. In the present study we used the olfactory bulbectomy (OBX) animal model of depression to assess the effects of the sigma1 ligand igmesine on OBX-induced behaviour. Behavioural experiments demonstrated OBX (saline-treated) rats to have increased dizocilpine-induced behavioural modifications, including locomotor and circling activity as compared to Sham rats (saline-treated). A short-term (7 d) treatment with low doses of igmesine (50-200 microg/kg.d s.c.) had no effect on dizocilpine-induced behaviour while long-term treatments (14 d) with low doses of igmesine reversed the effect of the bulbectomy such that the treated OBX rats' behaviour was not significantly different from Sham-saline rats. Short-term treatments with high doses of igmesine (500-1000 microg/kg.d) also reversed the increased locomotor and circling behaviour seen in OBX rats (saline-treated) while long-term treatments with the same high doses did not. These results provide behavioural evidence for sigma ligand's potential to reverse some OBX-induced behaviours. Moreover, they support the notion of a bell-shaped dose-response curve previously reported for sigma ligands.
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PMID:Effects of sigma ligands on NMDA receptor function in the bulbectomy model of depression: a behavioural study in the rat. 1205 32

Little is known regarding the functional processes underlying the treatment efficacy of antidepressant drugs. Given the close association between stress, anxiety and depression, distinguishing the common and disparate features of these processes may contribute to our current understanding. Using the olfactory bulbectomized (OBX) rat, an animal model sensitive to a variety of antidepressant drugs, this study examined the effects of chronic fluoxetine administration on open-field behavior under different conditions of stressfulness (luminance) and compared the fluoxetine effects to those evoked by the anxiolytic lorazepam. Sham-operated and OBX rats received 21 daily injections of fluoxetine (10 mg/kg), one or seven injections of lorazepam (0.1 and 0.5 mg/kg) or vehicle prior to testing in the open field or plus maze. Time series data were collected and fit with exponential regression models to estimate behavioral reactivity, habituation and residual rate of responding. Relative to sham controls, OBX rats displayed increased locomotor activity in the high luminance open field but showed decreased activity in the lower luminance open field. Time series analysis revealed that while sham animals showed increased habituation in the high compared to lower luminance open field, OBX rats did not significantly modify their responding between the two conditions. Chronic fluoxetine treatment invoked rectifying effects in OBX animals only in the high luminance open field by increasing the rate of habituation. Both acute and subchronic administration of lorazepam also reduced OBX hyperactivity but did so only by decreasing the residual rate of responding. As expected, lorazepam administration significantly increased the ratio of open-to-total arm activity in the elevated plus maze. These findings suggest that OBX responding in the open field may be maladaptive, reflecting an inability to modify behavior appropriately in certain environmental contexts. Chronic antidepressant treatment enhances habituation of OBX animals only under more stressful or aversive conditions and appears to do so in a manner temporally distinct from anxiolytic treatment.
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PMID:Fluoxetine-induced increases in open-field habituation in the olfactory bulbectomized rat depend on test aversiveness but not on anxiety. 1215 Oct 47


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