BACKGROUND: An imbalance between neuropeptides that promote stress and resilience, such as corticotropin-releasing factor and nociceptin, has been postulated to underlie relapse in addiction. The objective of this study was to develop a paradigm to image the in vivo interaction between stress-promoting neuropeptides and nociceptin (NOP) receptors in humans. METHODS: [11C]NOP-1A positron emission tomography was used to measure the binding to NOP receptors at baseline (BASE) and following an intravenous hydrocortisone challenge (CORT) in 19 healthy control subjects. Hydrocortisone was used as a challenge because in microdialysis studies it has been shown to increase corticotropin-releasing factor release in extrahypothalamic brain regions such as the amygdala. [11C]NOP-1A total distribution volume (VT) in 11 regions of interest were measured using a 2-tissue compartment kinetic analysis. The primary outcome measure was hydrocortisone-induced ΔVT calculated as (VT CORT - VT BASE)/VT BASE. RESULTS: Hydrocortisone led to an acute increase in plasma cortisol levels. Regional [11C]NOP-1A VT was on average 11% to 16% higher in the post-hydrocortisone condition compared with the baseline condition (linear mixed model, condition, p = .005; region, p < .001; condition × region, p < .001). Independent Student's t tests in all regions of interest were statistically significant and survived multiple comparison correction. Hydrocortisone-induced ΔVT was significantly negatively correlated with baseline VT in several regions of interest. CONCLUSIONS: Hydrocortisone administration increases NOP receptor availability. Increased NOP in response to elevated cortisol might suggest a compensatory mechanism in the brain to counteract corticotropin-releasing factor and/or stress. The [11C]NOP-1A and hydrocortisone imaging paradigm should allow for the examination of interactions between stress-promoting neuropeptides and NOP in addictive disorders.
BACKGROUND: An imbalance between neuropeptides that promote stress and resilience, such as corticotropin-releasing factor and nociceptin, has been postulated to underlie relapse in addiction. The objective of this study was to develop a paradigm to image the in vivo interaction between stress-promoting neuropeptides and nociceptin (NOP) receptors in humans. METHODS: [11C]NOP-1A positron emission tomography was used to measure the binding to NOP receptors at baseline (BASE) and following an intravenous hydrocortisone challenge (CORT) in 19 healthy control subjects. Hydrocortisone was used as a challenge because in microdialysis studies it has been shown to increase corticotropin-releasing factor release in extrahypothalamic brain regions such as the amygdala. [11C]NOP-1A total distribution volume (VT) in 11 regions of interest were measured using a 2-tissue compartment kinetic analysis. The primary outcome measure was hydrocortisone-induced ΔVT calculated as (VT CORT - VT BASE)/VT BASE. RESULTS: Hydrocortisone led to an acute increase in plasma cortisol levels. Regional [11C]NOP-1A VT was on average 11% to 16% higher in the post-hydrocortisone condition compared with the baseline condition (linear mixed model, condition, p = .005; region, p < .001; condition × region, p < .001). Independent Student's t tests in all regions of interest were statistically significant and survived multiple comparison correction. Hydrocortisone-induced ΔVT was significantly negatively correlated with baseline VT in several regions of interest. CONCLUSIONS: Hydrocortisone administration increases NOP receptor availability. Increased NOP in response to elevated cortisol might suggest a compensatory mechanism in the brain to counteract corticotropin-releasing factor and/or stress. The [11C]NOP-1A and hydrocortisone imaging paradigm should allow for the examination of interactions between stress-promoting neuropeptides and NOP in addictive disorders.
Authors: Rajesh Narendran; N Scott Mason; Maureen A May; Chi-Min Chen; Steve Kendro; Khanum Ridler; Eugenii A Rabiner; Marc Laruelle; Chester A Mathis; W Gordon Frankle Journal: Synapse Date: 2011-01 Impact factor: 2.562
Authors: Talakad G Lohith; Sami S Zoghbi; Cheryl L Morse; Maria F Araneta; Vanessa N Barth; Nancy A Goebl; Johannes T Tauscher; Victor W Pike; Robert B Innis; Masahiro Fujita Journal: J Nucl Med Date: 2012-02-06 Impact factor: 10.057
Authors: Victor W Pike; Karen S Rash; Zhaogen Chen; Concepción Pedregal; Michael A Statnick; Yasuyuki Kimura; Jinsoo Hong; Sami S Zoghbi; Masahiro Fujita; Miguel A Toledo; Nuria Diaz; Susan L Gackenheimer; Johannes T Tauscher; Vanessa N Barth; Robert B Innis Journal: J Med Chem Date: 2011-03-25 Impact factor: 7.446
Authors: Rajesh Narendran; W Gordon Frankle; N Scott Mason; Eugenii A Rabiner; Roger N Gunn; Graham E Searle; Shivangi Vora; Maralee Litschge; Steve Kendro; Thomas B Cooper; Chester A Mathis; Marc Laruelle Journal: Synapse Date: 2009-06 Impact factor: 2.562
Authors: Talakad G Lohith; Sami S Zoghbi; Cheryl L Morse; Maria D Ferraris Araneta; Vanessa N Barth; Nancy A Goebl; Johannes T Tauscher; Victor W Pike; Robert B Innis; Masahiro Fujita Journal: Neuroimage Date: 2013-11-10 Impact factor: 6.556
Authors: Victor A D Holanda; Matheus C Oliveira; Edilson D Da Silva Junior; Girolamo Calo'; Chiara Ruzza; Elaine C Gavioli Journal: Neurobiol Stress Date: 2020-10-05