The International Journal of Neuropsychopharmacology



Gender and age affect NK1 receptors in the human brain – a positron emission tomography study with [18F]SPA-RQ


Mikko J. Nyman a1, Olli Eskola a2, Jaana Kajander a1, Tero Vahlberg a3, Sandra Sanabria a4, Donald Burns a4, Richard Hargreaves a4, Olof Solin a2 and Jarmo Hietala a1a5c1
a1 Turku PET Centre, Neuropsychiatric Imaging, Turku, Finland
a2 Turku PET Centre, Accelerator Laboratory, Turku, Finland
a3 Department of Biostatistics, University of Turku, Turku, Finland
a4 Imaging Research, Merck Research Laboratories, West Point, PA, USA
a5 Department of Psychiatry, Turku University Central Hospital, Turku, Finland

Article author query
nyman mj   [PubMed][Google Scholar] 
eskola o   [PubMed][Google Scholar] 
kajander j   [PubMed][Google Scholar] 
vahlberg t   [PubMed][Google Scholar] 
sanabria s   [PubMed][Google Scholar] 
burns d   [PubMed][Google Scholar] 
hargreaves r   [PubMed][Google Scholar] 
solin o   [PubMed][Google Scholar] 
hietala j   [PubMed][Google Scholar] 

Abstract

Substance P (SP) is a neurotransmitter and neuromodulator that mediates its effects in the brain predominantly via the neurokinin-1 receptors (NK1Rs). NK1Rs and SP have been shown clinically to be involved in nausea and emesis after chemotherapy (CINV) and have been implicated preclinically in a range of neuropsychiatric disorders but unlike CINV their blockade in these conditions does not have proven clinical value. We investigated whether age and gender affects NK1R binding potential (NK1R-BP; an index of receptor availability) in the living human brain using PET and [18F]SPA-RQ, a highly specific NK1R antagonist. Forty-five healthy volunteers (35 male and 10 female), aged between 19 and 55 years were studied. NK1R-BP was estimated using the simplified reference tissue model with cerebellum as a reference region. A regression analysis indicated that that a loss of NK1R is associated with normal ageing as shown by decreased NK1R-BP (average rate 7% per decade). Statistically significant negative associations between age and NK1R-BP were observed in temporal, parietal and frontal cortex, hippocampus and parahippocampal formation. In addition preliminary data were obtained suggesting possible gender differences in NK1R-BP in the cortex and putamen with females having a lower NK1R-BP. The exact physiological significance of these results remains to be elucidated but conceptually they could be involved in age-related CNS disorders or those with gender differences in prevalence.

(Received September 5 2005)
(Reviewed November 2 2005)
(Revised January 25 2006)
(Accepted January 25 2006)


Key Words: Age factors; gender factors; human; in vivo; NK1 receptor; positron emission tomography; substance P.

Correspondence:
c1 Professor of Psychiatry, Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, Building 9, 20700-Turku, Finland. Tel.: +358-2-269 2520 Fax: +358-2-269 2528 E-mail: jahi@utu.fi