Effects of selective 5-HT1A receptor antagonists on regional serotonin synthesis in the rat brain: An autoradiographic study with α-[14C]methyl-l-tryptophan

Tohyama, Yoshihiro; Yamane, Fumitaka; Merid, Maraki Fikre; Dikšić, Mirko

doi:10.1016/s0924-977x(01)00076-1

Cited by 38 publications

(32 citation statements)

References 46 publications

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“…Our results of a regional specific effect of acute fluvoxamine application on 5-HT synthesis rates, with a decrease in the raphe area and an increase in the nerve terminals is in line with the opposite effect i.e. increased 5-HT synthesis rate in the raphe and decreased rate in the nerve terminals, after acute administration of the pure 5-HT 1A antagonist, WAY100635, on regional 5-HT synthesis [29].…”

Section: Discussionsupporting

confidence: 85%

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Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

Mück‐Šeler

Pivac

Dikšić

2012

Nuclear Medicine and Biology

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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

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Section: Discussionsupporting

confidence: 85%

“…We have published numerous papers that included the set of representative autoradiograms [4,21,22,[28][29][30]. Given this, and the fact that there is little information of value provided by this set, we did not include them in the current paper.…”

Section: Resultsmentioning

confidence: 99%

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

Mück‐Šeler

Pivac

Dikšić

2012

Nuclear Medicine and Biology

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“…The presence of higher densities of 5-HT 1B receptors in the FSL rats [30], despite the lack of significant differences in the extracellular 5-HT levels [57] may suggest a different sensitivity of these receptors in the FRL and FSL strains. The 5-HT 1A receptors, which also control the synthesis [50] and release of 5-HT as do the 5-HT 1B receptors, show lower sensitivity [46] in the FSL rats, relative to the FRL and SPD rats. It should be noted that the autoradiographic method used by [30] could not distinguish the relative contributions of the auto-and heteroreceptor pools of 5-HT 1B to the increased density of the 5-HT 1B receptors in the FSL rats, as the 5-HT 1B terminal auto-and heteroreceptors are found in the same 5-HT projecting regions [4,29] and no ligand, so far, has shown sufficient binding selectivity for one of these receptor pools.…”

Section: Discussionmentioning

confidence: 93%

“…It has been shown that both types of 5-HT receptors with altered densities in the FSL rats (5-HT 1A and 5-HT 1B ) are involved in the control of 5-HT synthesis [9,50]. The 5-HT 1B receptor is localized at the synaptic terminals of the 5-HT neurons, where it serves as an autoreceptor involved in the regulation of 5-HT neuron functioning.…”

Section: Introductionmentioning

confidence: 99%

The opposite effect of a 5-HT1B receptor agonist on 5-HT synthesis, as well as its resistant counterpart, in an animal model of depression

Skelin

Kovačević

Sato

et al. 2012

Brain Research Bulletin

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Flinders Sensitive Line (FSL) rat is as an animal model of depression with altered parameters of the serotonergic (5-HT) system function (5-HT synthesis rates, tissue concentrations, release, receptor density and affinity), as well as an altered sensitivity of these parameters to different 5-HT based antidepressants. The effects of acute and chronic treatments with the 5-HT 1B agonist, CP-94253 on 5-HT synthesis, in the FSL rats and the Flinders Resistant Line (FRL) controls were measured using α-[ 14 C]methyl-L-tryptophan (α-MTrp) autoradiography. CP-94253 (5 mg/kg), or an adequate volume of saline, was injected i.p. as a single dose in the acute experiment or delivered via the subcutaneously implanted osmotic minipump (5 mg/kg/day for 14 days) in the chronic experiment. The acute treatment with CP-94253 significantly decreased the 5-HT synthesis in both the FRL and FSL rats, with a more widespread effect in the FRL rats. Chronic treatment with CP-94253 significantly decreased 5-HT synthesis in the FRL rats, while 5-HT synthesis in the FSL rats was significantly increased throughout the brain. In both the acute and chronic experiment, the FRL rats had higher brain 5-HT synthesis rates, relative to the FSL rats.The shift in the direction of the treatment effect from acute to chronic, using the 5-HT 1B agonist, CP-94253, on 5-HT synthesis in the FSL model of depression, with an opposite effect on the control FRL rats, suggests the differential adaptation of the 5-HT system in the FSL and FRL rats to chronic stimulation of 5-HT 1B receptors.

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“…This suggests a different coupling of 5-HT 2A receptors with the second messengers than those of 5-HT 1A , because at the latter receptors, agonists reduced [52,75], and antagonists [74] elevated, regional 5-HT synthesis. …”

Section: Discussionmentioning

confidence: 99%

5-HT2A receptor antagonist M100907 reduces serotonin synthesis: An autoradiographic study

Hasegawa

Fikre-Merid

Dikšić

2012

Brain Research Bulletin

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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.

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Effects of selective 5-HT1A receptor antagonists on regional serotonin synthesis in the rat brain: An autoradiographic study with α-[14C]methyl-l-tryptophan

Cited by 38 publications

References 46 publications

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

The opposite effect of a 5-HT1B receptor agonist on 5-HT synthesis, as well as its resistant counterpart, in an animal model of depression

5-HT2A receptor antagonist M100907 reduces serotonin synthesis: An autoradiographic study

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