Abstract:There is no significant global or individual structure difference in the synthesis between the Sham-CTP and OBX-CTP groups. The similarity in the synthesis between the OBX-CTP, Sham-CTP and Sham-SAL groups is likely a result of changes in the sensitivity of the receptors through which 5-HT synthesis is controlled. Because of some of the differences in the synthesis between the Sham-CTP and Sham-SAL groups, the data suggest that receptors throughout the brain are not fully desensitized.
“…We have shown that elevated 5-HT synthesis rates in an animal model of depression, olfactory bulbectomized (OBX) rats, were normalized following chronic SSRI treatment [30]. It was thought that normalized 5-HT synthesis rates resulted in the desensitization of the 5-HT 1A receptor [30].…”
Section: Discussionmentioning
confidence: 99%
“…A set of representative autoradiograms illustrating 5-HT synthesis in the rat brain as determined by the α-MTrp method have been presented in many previous publications [49,37,24,52,75,30,31] and their addition would not provide any new information, because the logarithmic scale between the tracer concentration (represented by 5-HT synthesis) and optical density. All that can be seen from these images is the brain non-homogenous distribution.…”
Section: Measurement Of the α-Mtrp Trapping And Calculation Of 5-ht Smentioning
confidence: 99%
“…All that can be seen from these images is the brain non-homogenous distribution. The resultant images on the X-ray film were analyzed using a microcomputerbased image analyzing system (MCID/M4-Image Analysis System, Imaging Research Inc., Canada) and tissue equivalent calibrated standards as detailed in previous publications [49,37,23,30]. The optical densities were converted into tissue radioactivity concentration (nCi/g).…”
Section: Measurement Of the α-Mtrp Trapping And Calculation Of 5-ht Smentioning
confidence: 99%
“…It is also important to investigate whether 5-HT 2A receptors play a role in the modulation of 5-HT synthesis, as the modulation of regional 5-HT synthesis appears to be part of antidepressant action [37,23,10,30,46]. This question was studied by investigating the influence of a selective 5-HT 2A antagonist, M100907.…”
The effects of the administration of the serotonin (5-HT) 2A antagonist, M100907, on 5-HT synthesis rates, were evaluated using the α-[ 14 C]methyl-L-tryptophan (α-MTrp) autoradiographic method. In the treatment study, M100907 (10 mg/kg) was injected intraperitoneally 30 min before the α-MTrp injection (30 μCi over 2 min). A single dose of M100907 caused a significant decrease in the synthesis in the anterior olfactory nucleus, accumbens nucleus, frontal cortex, sensory-motor cortex, cingulate cortex, medial caudate-putamen, dorsal thalamus, substantia nigra, inferior collicus, raphe magnus nucleus, superior olive, and raphe pallidus nucleus.These data suggest that the terminal 5-HT 2A receptors are involved in the regulation of 5-HT synthesis in the entire brain. Further, 5-HT synthesis is likely regulated by the 5-HT 2A antagonistic property of M100907 in the cortices, anterior olfactory nucleus, caudate putamen, and nucleus accumbens.
“…We have shown that elevated 5-HT synthesis rates in an animal model of depression, olfactory bulbectomized (OBX) rats, were normalized following chronic SSRI treatment [30]. It was thought that normalized 5-HT synthesis rates resulted in the desensitization of the 5-HT 1A receptor [30].…”
Section: Discussionmentioning
confidence: 99%
“…A set of representative autoradiograms illustrating 5-HT synthesis in the rat brain as determined by the α-MTrp method have been presented in many previous publications [49,37,24,52,75,30,31] and their addition would not provide any new information, because the logarithmic scale between the tracer concentration (represented by 5-HT synthesis) and optical density. All that can be seen from these images is the brain non-homogenous distribution.…”
Section: Measurement Of the α-Mtrp Trapping And Calculation Of 5-ht Smentioning
confidence: 99%
“…All that can be seen from these images is the brain non-homogenous distribution. The resultant images on the X-ray film were analyzed using a microcomputerbased image analyzing system (MCID/M4-Image Analysis System, Imaging Research Inc., Canada) and tissue equivalent calibrated standards as detailed in previous publications [49,37,23,30]. The optical densities were converted into tissue radioactivity concentration (nCi/g).…”
Section: Measurement Of the α-Mtrp Trapping And Calculation Of 5-ht Smentioning
confidence: 99%
“…It is also important to investigate whether 5-HT 2A receptors play a role in the modulation of 5-HT synthesis, as the modulation of regional 5-HT synthesis appears to be part of antidepressant action [37,23,10,30,46]. This question was studied by investigating the influence of a selective 5-HT 2A antagonist, M100907.…”
The effects of the administration of the serotonin (5-HT) 2A antagonist, M100907, on 5-HT synthesis rates, were evaluated using the α-[ 14 C]methyl-L-tryptophan (α-MTrp) autoradiographic method. In the treatment study, M100907 (10 mg/kg) was injected intraperitoneally 30 min before the α-MTrp injection (30 μCi over 2 min). A single dose of M100907 caused a significant decrease in the synthesis in the anterior olfactory nucleus, accumbens nucleus, frontal cortex, sensory-motor cortex, cingulate cortex, medial caudate-putamen, dorsal thalamus, substantia nigra, inferior collicus, raphe magnus nucleus, superior olive, and raphe pallidus nucleus.These data suggest that the terminal 5-HT 2A receptors are involved in the regulation of 5-HT synthesis in the entire brain. Further, 5-HT synthesis is likely regulated by the 5-HT 2A antagonistic property of M100907 in the cortices, anterior olfactory nucleus, caudate putamen, and nucleus accumbens.
“…Several neurochemical and behavioural studies [3][4][5] have found alterations in serotonergic neurotransmission after treatment with various classes of antidepressant drugs, including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRI), such as fluvoxamine [6].…”
Introduction-A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression.Methods-The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14 C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi).Results-There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini-Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (−32%), but not in the median (−14%) and dorsal (−3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%).Conclusions-The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors.
Keywords
Rationale Anhedonia is a core symptom of major depression. Deficits in reward function, which underlie anhedonia, can be readily assessed in animals. Therefore, anhedonia may serve as an endophenotype for understanding the neural circuitry and molecular pathways underlying depression.Objective Surprisingly, there is scant knowledge regarding alterations in brain reward function after olfactory bulbectomy (OB), an animal model which results in a behavioural syndrome responsive to chronic antidepressant treatment. Therefore, the present studies aimed to assess reward function after bulbectomy. Materials and methods The present study utilized sucrose preference, cocaine-induced hyperlocomotion and intracranial self-stimulation (ICSS) responding to examine reward processes in the OB model.Results Bulbectomized animals showed a marked preference (>90%) for 0.8% sucrose solution compared with water; similar to the preference exhibited by sham controls. Importantly, there were pronounced deficits in brain reward function, as assessed using ICSS, which lasted 8 days before returning to baseline levels. Furthermore, bulbectomized animals were hyper-responsive to the locomotor stimulating properties of an acute and a repeated cocaine regimen. However, no difference in ICSS facilitation was observed in response to an acute cocaine injection. Conclusions Taken together, these results suggest that bulbectomized rats display alterations in brain reward function, but these changes are not long-lasting and thus, not amenable to investigating the effects of pharmacological interventions. However, given that OB animals are hypersensitive to drugs of abuse, bulbectomy may be an appropriate inducing factor for the development of animal models of co-morbid depression and drug dependence.
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