Quantitative radioluminography of serotonin uptake sites in the porcine brain

Cumming, Paul; Kretzschmar, Marion; Brust, Peter; Smith, Donald F.

doi:10.1002/1098-2396(20010315)39:4<351::aid-syn1019>3.0.co;2-m

Cited by 15 publications

(4 citation statements)

References 29 publications

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“…The innervation displayed by the fine fibers in the neocortical areas 17 and 36 points, on the other hand, towards nonsynaptic volume transmission and thus a general and diffuse modulation of the neural activity herein (Agnati et al 1995;Vizi and Kiss 1998;Gulya´s et al 1999). The proposed close relation between the serotonergic system and the retrohippocampal areas, as opposed to the neighboring neocortical area, is furthermore substantiated by findings demonstrating that the entorhinal cortex contains the highest levels of serotonin, serotonin reuptake sites and 5HT 3 -receptors, as compared to other cortical areas in rats and pigs (Langlais et al 1987;Kilpatrick et al 1989;Dewar et al 1991;Cumming et al 2001).…”

Section: Discussionmentioning

confidence: 81%

Distribution and morphology of serotonin-immunoreactive axons in the retrohippocampal areas of the New Zealand white rabbit

2005

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This study provides a detailed light microscopic description of the morphology and distribution of serotonin-immunoreactive axons in the paleocortical retrohippocampal areas, viz. the subiculum, presubiculum, parasubiculum and entorhinal area, and the adjoining neocortical perirhinal and retrosplenial cortices of the New Zealand white rabbit. Serotonergic axons could be segregated into three different fiber types named fine fibers, beaded fibers and stem-axons. Fine fibers were evenly distributed thin axons with small fusiform/granular varicosities. Beaded fibers were thin axons with large varicosities, predominantly located in the retrohippocampal supragranular layers, where they often formed pericellular arrays. Stem-axons were thick straight, nonvaricose axons seen in the white matter of psalterium dorsale, alveus and the plexiform layer. The paleocortical retrohippocampal areas had a dense supragranular innervation with numerous tortuous fine and beaded fibers, intermingled in conglomerates with conspicuous varicosities forming pericellular arrays. In contrast, the neocortical area 17 and the lateral part of the perirhinal cortex (area 36) were innervated by evenly distributed fine fibers with a moderate number of small varicosities and few ramifications, whereas, the retrosplenial cortex (areas 29e, 29ab and 29cd), and the medial part of the perirhinal cortex (area 35) displayed an intermediate innervation pattern, probably reflecting the transitional nature of these areas being located between the paleo- and the neocortex. The described dualistic innervation pattern may functionally enable the serotonergic system to exert a strong influence on the supragranular layers of the retrohippocampal areas and thus on the neural input entering these areas from the perirhinal and neighboring polymodal association neocortices, whereas the innervation pattern in the adjoining neocortical areas points towards a more diffuse and general modulation of neural activity herein.

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Section: Discussionmentioning

confidence: 81%

Distribution and morphology of serotonin-immunoreactive axons in the retrohippocampal areas of the New Zealand white rabbit

2005

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“…For application of longer acquisition protocols and its use in satellite PET facilities, McN5652 was successfully labeled with 18 F [108] and tested in animals in vivo. In autoradiographic studies [ 18 F](+)-FMe-McN5652 showed the typical SERT distribution pattern [109,110] and was displaceable by SERT uptake inhibitors [109,111,112]. From Because of its binding to other monoaminergic transporters, the [ 123 I] -CIT uptake in the striatum mostly reflects dopamine transporter, whereas the PET uptake patterns are specific for SERT.…”

Section: Radioligands For Serotonin Transporter Imaging In Humansmentioning

confidence: 99%

Neuroimaging of the Serotonin Transporter: Possibilities and Pitfalls

Brust¹,

Hesse²,

Müller³

et al. 2006

CPSR

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Nuclear medicine imaging techniques like positron emission tomography (PET) and single-photon emission computed tomography (SPECT) apply radiolabeled drugs that bind selectively to specific neurotransmitter receptors and transporters such as the serotonin transporter (SERT) in the living human brain. They can help overcome certain limitations of postmortem, platelet and genetic studies of the SERT. This review compares the outcome of those studies with recent neuroimaging findings. The first part of this review deals with the choice of radioligands used to quantify SERT distribution in the human brain. The second part summarizes studies performed to understand the normal physiology of the serotonergic system. Selective serotonin reuptake inhibitors (SSRIs), used to treat a wide range of neuropsychiatric disorders with emotional instability and behavioral control deficits, compete with SERT radioligands and have been investigated in pharmacological PET and SPECT studies in healthy volunteers and patients. Part three reviews SERT imaging studies in patients, which have meanwhile been performed in most disorders that benefit from SSRI treatment. It is hypothesized that serotonin deficits and neuropsychiatric symptoms are linked by the inhibition of involuntary emotional reactions to external and internal stimuli. This could explain, why the consistency of many SERT neuroimaging findings is low, and may help develop individual treatment strategies in therapy-nonresponsive cases and to engineer new drugs for the therapy of neuropsychiatric disorders.

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“…The binding parameter f 1 BP (obtained from the unconstrained fit) was found to be the one that correlates best with the SERT density, as determined by in vitro autoradiography with [ 3 H]citalopram on the porcine brain (Cumming et al, 2001;Kretzschmar et al, 2003). This highly significant correlation is shown in Figure 7 for both radiotracers.…”

Section: Coronalmentioning

confidence: 74%

In vivo Measurement of the Serotonin Transporter with (S)-([18F]fluoromethyl)-(+)-McN5652

Brust¹,

Hinz

Kuwabara

et al. 2003

Neuropsychopharmacol

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The radiolabeled serotonin transporter (SERT) ligand [ 11 C](+)-McN5652 has recently been used in clinical positron emission tomography (PET) studies for SERT imaging. However, this radioligand offers disadvantages in routine clinical settings because of its short radioisotope half-life (eg PET facilities within hospitals without a cyclotron need to acquire such radioligands from distant cyclotron units for clinical use).is an analogue which has been synthesized newly, and has a significantly longer radioisotope half-life. In the porcine brain, it demonstrates the same characteristic distribution pattern of serotonin-uptake sites like the 11 C-labeled congener with the highest binding in the midbrain and thalamus and the lowest in the cerebellum and occipital cortex. It shows a 30% higher blood-brain transfer and a slower peripheral metabolism than

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Quantitative radioluminography of serotonin uptake sites in the porcine brain

Cited by 15 publications

References 29 publications

Distribution and morphology of serotonin-immunoreactive axons in the retrohippocampal areas of the New Zealand white rabbit

Distribution and morphology of serotonin-immunoreactive axons in the retrohippocampal areas of the New Zealand white rabbit

Neuroimaging of the Serotonin Transporter: Possibilities and Pitfalls

In vivo Measurement of the Serotonin Transporter with (S)-([18F]fluoromethyl)-(+)-McN5652

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