MicroPET imaging of 5-HT1A receptors in rat brain: a test–retest [18F]MPPF study
- 244 Downloads
Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [18F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine1A (5-HT1A) receptors in different regions of animal and human brain, including that of 5-HT1A 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).
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.
Values 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.
MicroPET brain imaging of 5-HT1A receptors with [18F]MPPF thus represents a promising avenue for investigating 5-HT1A receptor function in rat.
KeywordsBinding potential Serotonin receptors Brain imaging Autoreceptors Positron emission tomography
The authors are grateful to Shadreck Mzengeza for his help with the radiochemistry. The work was funded by the Canadian Institutes for Health Research (operating grants to C.B. and L.D.). N.A. held a postdoctoral fellowship, and L.D. benefitted from an infrastructure grant from the Fonds de la Recherche en Santé du Québec.
Conflict of interest
The authors declare that they have no competing financial interests.
- 2.Frazer AHJ. Serotonin. Philadelphia: Lippincott-Raven; 1999.Google Scholar
- 3.Dahlström A, Fuxe K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl. 1964;232:231–55.Google Scholar
- 9.Roth B. The serotonin receptors: from molecular pharmacology to human therapeutics. Totowa: Humana; 2006.Google Scholar
- 21.Plenevaux A, Weissmann D, Aerts J, Lemaire C, Brihaye C, Degueldre C, et al. Tissue distribution, autoradiography, and metabolism of 4-(2¢-methoxyphenyl)-1-[2′ -[N-2′-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: an in vivo study in rats. J Neurochem. 2000;75:803–11.PubMedCrossRefGoogle Scholar
- 24.Riad M, Zimmer L, Rbah L, Watkins KC, Hamon M, Descarries L. Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18F]MPPF in the nucleus raphe dorsalis of rat. J Neurosci. 2004;24:5420–6.PubMedCrossRefGoogle Scholar
- 27.Sibon I, Benkelfat C, Gravel P, Aznavour N, Costes N, Mzengeza S, et al. Decreased [(18)F]MPPF binding potential in the dorsal raphe nucleus after a single oral dose of fluoxetine: a positron-emission tomography study in healthy volunteers. Biol Psychiatry. 2008;63:1135–40.PubMedCrossRefGoogle Scholar
- 36.Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th ed. New York: Academic; 1998.Google Scholar
- 48.Parsey RV, Slifstein M, Hwang DR, Abi-Dargham A, Simpson N, Mawlawi O, et al. Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans: comparison of arterial and reference tissue input functions. J Cereb Blood Flow Metab. 2000;20:1111–33.PubMedCrossRefGoogle Scholar
- 54.Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O’Laughlin IA, Meltzer HY. 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem. 2001;76:1521–31.PubMedCrossRefGoogle Scholar