In vivo mapping of substance P receptors in brains of laboratory animals by high-resolution imaging systems

Synapse
Eisuke HanedaTetsuya Suhara

Abstract

Neurotransmission mediated by substance P (SP) and NK(1) receptor has been implicated in the pathophysiology of analgesia, emesis and diverse neuropsychiatric conditions including depression and anxiety disorder. Several lines of clinical trials using NK(1) receptor antagonists have been conducted to date, and the efficiency of preclinical assessments for proof of concept and dose optimization could be greatly increased by configuring an in vivo analytical system that permits quantitative mapping of NK(1) receptors in the brains of small-size laboratory animals expressing "human-like" NK(1) receptors. Hence, we investigated the applicability of experimental animals, ranging from rodents to primates, to positron emission tomographic (PET) measurements with [(18)F]fluoroethyl-SPA-RQ, a modification of a recently established radioligand for NK(1) receptors. A pharmacokinetic assay could be performed for a rhesus monkey in an awake condition, which allows the circumvention of influences of anesthesia on SP neurotransmission. Coregistration of PET and magnetic resonance images acquired by small-animal-dedicated devices enabled detailed localization of NK(1) receptors in the gerbil and marmoset brains. The present study also revealed...Continue Reading

References

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Citations

Jul 2, 2009·Psychiatry and Clinical Neurosciences·Ling LiYumin Luo
Feb 8, 2011·Neuropeptides·Susan L Gackenheimer, Donald R Gehlert
Jan 23, 2015·The International Journal of Neuropsychopharmacology·Tadashi EndoMakoto Higuchi
Jun 20, 2014·Experimental and Therapeutic Medicine·Xiao-Wei JiDian-Yun Wang
Dec 3, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stina SyvänenMargareta Hammarlund-Udenaes
Sep 5, 2019·Pharmaceutics·Agnieszka Majkowska-PilipEwa Gniazdowska

Related Concepts

(18F)SPA-RQ
Autoradiography
Brain
Functional Cerebral Localization
Fluorine Radioisotopes
Optical Image Reconstruction
Piperidines
Primates
Family Dipodidae
Hypothalamic Substance P

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