OBJECTIVES: The role of the norepinephrine transporter (NET) in cocaine dependence has never been demonstrated via in vivo imaging due to the lack of suitable NET radioligands. Here we report our preliminary studies evaluting the NET in individuals with cocaine dependence (COC) in comparison to healthy controls (HC) using (S,S)-[(11)C]methylreboxetine ([(11)C]MRB), the most promising C-11 labeled positron-emission tomography (PET) radioligand for NET developed to date. METHODS: Twenty two human volunteers (10 COC and 12 HC) underwent dynamic (11)C-MRB-PET acquisition using a High Resolution Research Tomograph (HRRT). Binding potential (BP(ND)) parametric images were computed using the simplified reference tissue model (SRTM2) with occipital cortex as reference region. BP(ND) values were compared between the two groups. RESULTS: Locus coeruleus (LC), hypothalamus, and pulvinar showed a significant inverse correlation with age among HC (age range = 25-54 years; P = 0.04, 0.009, 0.03 respectively). The BP(ND) was significantly increased in thalamus (27%; P < 0.02) and dorsomedial thalamic nuclei (30%; P < 0.03) in COC as compared to HC. Upon age normalization, the upregulation of NET in COC also reached significance in LC (63%, P < 0.01) and pulvinar (55%, P < 0.02) regions. CONCLUSION: Our results suggest that (a) brain NET concentration declines with age in HC, and (b) there is a significant upregulation of NET in thalamus and dorsomedial thalamic nucleus in COC as compared to HC. Our results also suggest that the use of [(11)C]MRB and HRRT provides an effective strategy for studying alterations of the NET system in humans.
OBJECTIVES: The role of the norepinephrine transporter (NET) in cocaine dependence has never been demonstrated via in vivo imaging due to the lack of suitable NET radioligands. Here we report our preliminary studies evaluting the NET in individuals with cocaine dependence (COC) in comparison to healthy controls (HC) using (S,S)-[(11)C]methylreboxetine ([(11)C]MRB), the most promising C-11 labeled positron-emission tomography (PET) radioligand for NET developed to date. METHODS: Twenty two human volunteers (10 COC and 12 HC) underwent dynamic (11)C-MRB-PET acquisition using a High Resolution Research Tomograph (HRRT). Binding potential (BP(ND)) parametric images were computed using the simplified reference tissue model (SRTM2) with occipital cortex as reference region. BP(ND) values were compared between the two groups. RESULTS: Locus coeruleus (LC), hypothalamus, and pulvinar showed a significant inverse correlation with age among HC (age range = 25-54 years; P = 0.04, 0.009, 0.03 respectively). The BP(ND) was significantly increased in thalamus (27%; P < 0.02) and dorsomedial thalamic nuclei (30%; P < 0.03) in COC as compared to HC. Upon age normalization, the upregulation of NET in COC also reached significance in LC (63%, P < 0.01) and pulvinar (55%, P < 0.02) regions. CONCLUSION: Our results suggest that (a) brain NET concentration declines with age in HC, and (b) there is a significant upregulation of NET in thalamus and dorsomedial thalamic nucleus in COC as compared to HC. Our results also suggest that the use of [(11)C]MRB and HRRT provides an effective strategy for studying alterations of the NET system in humans.
Authors: Jesse R Schank; Rossella Ventura; Stefano Puglisi-Allegra; Antonio Alcaro; Charlene D Cole; L Cameron Liles; Philip Seeman; David Weinshenker Journal: Neuropsychopharmacology Date: 2005-12-14 Impact factor: 7.853
Authors: N D Volkow; G J Wang; J S Fowler; S J Gatley; Y S Ding; J Logan; S L Dewey; R Hitzemann; J Lieberman Journal: Proc Natl Acad Sci U S A Date: 1996-09-17 Impact factor: 11.205
Authors: Kirsten Leineweber; Thekla Wangemann; Christine Giessler; Heike Bruck; Stefan Dhein; Martin Kostelka; Friedrich Wilhelm Mohr; Rolf Edgar Silber; Otto Erich Brodde Journal: J Am Coll Cardiol Date: 2002-10-16 Impact factor: 24.094
Authors: N D Volkow; Y S Ding; J S Fowler; G J Wang; J Logan; J S Gatley; S Dewey; C Ashby; J Liebermann; R Hitzemann Journal: Arch Gen Psychiatry Date: 1995-06
Authors: J Melasch; M Rullmann; A Hilbert; J Luthardt; G A Becker; M Patt; A Villringer; K Arelin; P M Meyer; D Lobsien; Y-S Ding; K Müller; O Sabri; S Hesse; B Pleger Journal: Int J Obes (Lond) Date: 2015-10-20 Impact factor: 5.095
Authors: Anne Vuorenpää; Trine N Jørgensen; Amy H Newman; Kenneth L Madsen; Mika Scheinin; Ulrik Gether Journal: J Biol Chem Date: 2016-01-19 Impact factor: 5.157
Authors: Shu-fei Lin; Xiaoning Fan; Catherine Weikart Yeckel; David Weinzimmer; Tim Mulnix; Jean-Dominique Gallezot; Richard E Carson; Robert S Sherwin; Yu-Shin Ding Journal: Nucl Med Biol Date: 2012-05-16 Impact factor: 2.408
Authors: Brian L Edlow; Emi Takahashi; Ona Wu; Thomas Benner; Guangping Dai; Lihong Bu; Patricia Ellen Grant; David M Greer; Steven M Greenberg; Hannah C Kinney; Rebecca D Folkerth Journal: J Neuropathol Exp Neurol Date: 2012-06 Impact factor: 3.685
Authors: Robert H Pietrzak; Jean-Dominique Gallezot; Yu-Shin Ding; Shannan Henry; Marc N Potenza; Steven M Southwick; John H Krystal; Richard E Carson; Alexander Neumeister Journal: JAMA Psychiatry Date: 2013-11 Impact factor: 21.596