Varnäs K, Halldin C, Hall H. Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain. Hum Brain Mapp 22: 246-260
Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden. Human Brain Mapping
(Impact Factor: 5.97).
08/2004; 22(3):246-60. DOI: 10.1002/hbm.20035
Several neurochemical in vitro and in vivo imaging studies have been aimed at characterizing the localization of serotonin receptors and transporters in the human brain. In this study, a detailed comparison of the distribution of a number of 5-HT receptor subtypes and the 5-HT transporter was carried out in vitro using human postmortem brain tissue. Anatomically adjacent whole hemisphere sections were incubated with specific radioligands for the 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(4) receptors and the 5-HT transporter. The autoradiograms revealed different laminar and regional distribution patterns in the isocortex, where 5-HT(1A) and 5-HT(4) receptor binding showed highest densities in superficial layers and 5-HT(2A) receptor binding was most abundant in middle layers. In cortical regions, 5-HT transporters were concentrated to several limbic lobe structures (posterior uncus, entorhinal, cingulate, insular and temporal polar regions). 5-HT(1A) receptor densities were also high in limbic cortical regions (hippocampus, posterior entorhinal cortex, and subcallosal area) compared to the isocortex. Subregionally different distribution patterns were observed in the basal ganglia with a trend toward higher levels in ventral striatal (5-HT(1B) receptors) and pallidal (5-HT transporters and 5-HT(1B) receptors) regions. The localization in regions belonging to limbic cortico-striato-pallido-thalamic circuits is in line with the documented role of 5-HT in modulation of mood and emotion, and the suggested involvement of this system in pathophysiology of various psychiatric disorders. The qualitative and quantitative information reported in this study might provide important complements to in vivo neuroimaging studies of the 5-HT system.
Available from: Yoshiteru Takekita
- "The serotonin 1A receptor (5-HT1AR) is another important receptor, since it has been implicated in both schizophrenia pathogenesis and antipsychotic mechanisms of action. 5-HT1AR is expressed in various sites throughout the brain such as the hippocampus (Barnes and Sharp, 1999; Aznar et al., 2003; Varnas et al., 2004), amygdala, and hypothalamus. A postmortem study including patients with schizophrenia demonstrated elevated 5-HT1AR density in the cortex of the frontal lobe (Hashimoto et al., 1991; Burnet et al., 1996; Sumiyoshi et al., 1996; Tauscher et al., 2002). "
- "The response to negative words was increased after intake of ATD in the superior temporal gyrus and posterior cingulate cortex. All of these brain regions have been implicated in the underlying pathophysiology of depression (Siegle et al. 2002;Drevets et al. 2002) and receive moderate-to-high densities of serotonergic projections from the dorsal and/or median raphé nuclei (Jacobs and Azmitia 1992;Varnäs et al. 2004). The response to emotional words after ATD intake was decreased in the right DLPFC as well as the right dACC, both of which are important in regulating 668 C. S.Biskup et al. "
[Show abstract] [Hide abstract]
ABSTRACT: Imbalances of neurotransmitter systems, particularly serotonin (5-HT) and dopamine (DA), are known to play an essential role in many neuropsychiatric disorders. The transient manipulation of such systems through the alteration of their amino acid precursors is a well-known research tool. Among these methods are alterations of tryptophan, the essential amino acid (AA) precursor of 5-HT, as well as manipulations of tyrosine and phenylalanine, the AA precursors of DA, which can be metabolized into norepinephrine and subsequently into epinephrine. These systems can be loaded by applying a large dose of these AAs or depleted by applying an amino acid mixture lacking the respective AAs serving as precursors. Functional neuroimaging has given insights into differential brain activation patterns and functions depending on the tasks performed, pharmacological treatments or specific disorders. Such research has shed light on the function of many brain areas as well as their interactions. The combination of AA challenge approaches with neuroimaging techniques has been subject of numerous studies. Overall, the studies conducted in this particular field of research have shown that AA challenge techniques are valid and effective research tools that allow the investigation of serotonergic and dopaminergic systems without causing serious side effects or long-term damage to the subjects. In this review, we will present an overview of the results obtained so far and discuss the implications of these findings as well as open questions that remain to be answered.
Available from: Markus Mitterhauser
- "particularly useful for voxel-wise analyses. Here, the clearance rate of the radiotracer from the reference region to plasma (k 2 ') was calculated from the insula (receptor-rich region) and cerebellar gray matter (receptor-poor region) (Ichise et al., 2003; Varnas et al., 2004) using the simplified reference tissue model 2 (Wu and Carson, 2002). These regions of interest were taken from an automated anatomical labeling-based atlas (Tzourio-Mazoyer et al., 2002; Savli et al., 2012), whereas the cerebellar gray matter (excluding vermis and sagittal sinus) served as reference region because of negligible specific receptor binding in this area as previously described (Hall et al., 1997; Hahn et al., 2010). "
[Show abstract] [Hide abstract]
ABSTRACT: Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role in the pathogenesis and treatment of anxiety to the serotonin-1A receptor (5-HT1A). To elucidate the effect of Silexan on 5-HT1A receptor binding, 17 healthy men underwent two positron emission tomography measurements using the radioligand [carbonyl-(11)C]WAY-100635 following the daily intake of 160 mg Silexan or placebo over a minimum of eight weeks, respectively (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. 5-HT1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared to placebo in two large clusters encompassing the temporal gyrus, the fusiform gyrus, the hippocampus on one hand as well as the insula and the anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. This PET study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan.
© The Author 2014. Published by Oxford University Press on behalf of CINP.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.