MicroPET imaging of 5-HT1A receptors in rat brain: a test–retest [18F]MPPF study

Abstract

Purpose Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [ 18 F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine 1A (5-HT 1A ) receptors in different regions of animal and human brain, including that of 5-HT 1A autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Methods Scans from isoflurane-anaesthetised rats (n=18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. ResultsValues of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. Conclusions MicroPET brain imaging of 5-HT 1A receptors with [18 F]MPPF thus represents a promising avenue for investigating 5-HT 1A receptor function in rat.

Serotonin 5-HT1A receptor binding sites in the brain of the pigeon (Columba livia)

“…Future studies are clearly needed to clarify the exact boundaries of different areas in the hippocampal formation of the avian species. The low overall density of 5-HT 1A receptors in the avian hippocampus is in contrast to that in rats and other mammals (Topic et al, 2007;Pazos and Palacios, 1985;Zilles et al, 1985Zilles et al, , 2000Wree et al, 1987;Zilles, 1989;Kraemer et al, 1995;Aznavour et al, 2009). …”

“…In contrast, all septal nuclei showed dense labeling that is in line with a strong serotonergic innervation in pigeons (Challet et al, 1996) and published 5-HT 1A receptor densities for cats, rats, non-human primates, and humans (Aznavour et al, 2009;Aznavour and Zimmer, 2007;Khawaja, 1995;Pazos and Palacios, 1985).…”

Serotonin Signaling through Prefrontal Cortex 5-HT1A Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors

“…Given our c-fos results and the literature on stress-coping strategies, we hypothesized that the phenotype might be due to effects in the mPFC. We also tested the dHP as an alternative effector region because it is one of the forebrain regions with the highest 5-HT 1A receptor expression (Aznavour et al, 2009; Aznavour et al, 2006; Descarries and Riad, 2012). …”

Applications of Small-Animal Imaging in Neurology and Psychiatry

“…The most promising evidence for a defi cit in central serotonin neurotransmission that is compensated by antidepressant pharmacotherapy involves postsynaptic serotonin-1A receptors (5-HT 1A ). In human PET studies, changes in expression and function of the 5-HT 1A receptor are well described, particularly in the mesiotemporal cortex and raphe nucleus (for review see [ 173 ] [ 175 ]. Test-retest variability was also in the order of 10 % in the larger brain regions and less than 20 % in small nuclei.…”