Abstract The olfactory bulbectomy in rodents has been proposed as an animal model for depression. According to the neurotrophin and monoamine hypotheses of depression, the present study examined ...neurotrophin and monoamine (serotonin, norepinephrine, dopamine) levels in several depression-related brain regions of mice subjected to olfactory bulbectomy. As expected, bulbectomized animals revealed behavioral alterations such as locomotor hyperactivity and reduced gain of bodyweight, regarded as correlates of a depressive-like state. Compared to sham-operated animals, bulbectomized mice demonstrated significantly increased brain-derived neurotrophic factor (BDNF), but regular nerve growth factor (NGF), protein levels in hippocampus (+ 108%) and frontal cortex (+ 48%) 16 days after olfactory bulbectomy. In these brain regions as well as in the hypothalamus, bulbectomy also caused a reduction of the molar ratio of 5-hydroxyindoleacetic acid to serotonin (5-HT) indicating a decrease in 5-HT turnover. Similarly, a hypofunction of the dopamine (DA) turnover was evident only in the hypothalamus in response to olfactory bulbectomy, presenting a decrease in the ratio 3,4 dihydroxyphenylacetic acid/DA with increased levels of DA. In all other brain areas investigated the levels of DA, its metabolite DOPAC and norepinephrine remained unaltered. Thus, olfactory bulbectomy seems to be a valid animal model also in mice related to serotonergic dysfunctions resembling bulbectomized rats that are a well-known model of hyposerotoninergic agitated depression. With respect to the common BDNF hypothesis of depression – predicting decreased BDNF expression in depression-related brain areas – the novel and challenging conclusions concern the increased BDNF protein levels in target regions of the cholinergic basal forebrain system in bulbectomized mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The 5-HT(4) receptor is a new potential target for antidepressant treatment and may be implicated in the pathogenesis of depression. This study investigated differences in 5-HT(4) receptor and 5-HT ...transporter (5-HTT) binding by quantitative autoradiography of (3)HSB207145 and (S)-N-methyl-(3)Hcitalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen. Among post hoc analyzed regions, there was a 14% decrease in 5-HT(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus. In comparison, GR(+/-) mice had increased 5-HT(4) receptor (11%) binding in the caudal caudate putamen and decreased 5-HTT binding in the frontal caudate putamen but no changes in dorsal and ventral hippocampus. Post hoc analysis showed increased 5-HT(4) receptor binding in the olfactory tubercles of GR(+/-) mice. In conclusion, we have found brain regional changes in 5-HT(4) receptor and 5-HTT transporter binding in two murine models of depression-related states, characterized by 5-HT and HPA system changes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The 5-HT sub(4) receptor is a new potential target for antidepressant treatment and may be implicated in the pathogenesis of depression. This study investigated differences in 5-HT sub(4) receptor ...and 5-HT transporter (5-HTT) binding by quantitative autoradiography of super(3)HSB207145 and (S)-N-methyl- super(3)Hcitalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR super(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR super(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT sub(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen. Among post hoc analyzed regions, there was a 14% decrease in 5-HT sub(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus. In comparison, GR super(+/-) mice had increased 5-HT sub(4) receptor (11%) binding in the caudal caudate putamen and decreased 5-HTT binding in the frontal caudate putamen but no changes in dorsal and ventral hippocampus. Post hoc analysis showed increased 5-HT sub(4) receptor binding in the olfactory tubercles of GR super(+/-) mice. In conclusion, we have found brain regional changes in 5-HT sub(4) receptor and 5-HTT transporter binding in two murine models of depression-related states, characterized by 5-HT and HPA system changes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The 5-HT
4 receptor is a new potential target for antidepressant treatment and may be implicated in the pathogenesis of depression. This study investigated differences in 5-HT
4 receptor and 5-HT ...transporter (5-HTT) binding by quantitative autoradiography of
3HSB207145 and (S)-N-methyl-
3Hcitalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR
+/−) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR
+/− mice have a deficit in hypothalamic–pituitary–adrenal (HPA) system control. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT
4 receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen. Among post hoc analyzed regions, there was a 14% decrease in 5-HT
4 receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus. In comparison, GR
+/− mice had increased 5-HT
4 receptor (11%) binding in the caudal caudate putamen and decreased 5-HTT binding in the frontal caudate putamen but no changes in dorsal and ventral hippocampus. Post hoc analysis showed increased 5-HT
4 receptor binding in the olfactory tubercles of GR
+/− mice. In conclusion, we have found brain regional changes in 5-HT
4 receptor and 5-HTT transporter binding in two murine models of depression-related states, characterized by 5-HT and HPA system changes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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