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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
Source: PubMed

ABSTRACT

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.

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    • "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). "

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    • "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. "
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    • "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). "
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