UNLABELLED: We have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [11C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. METHODS: PET was used to compare and characterize [11C]cocaine binding in the baboon brain at low subpharmacological (18 micrograms average dose) and at pharmacological (8000 micrograms) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). RESULTS: At subpharmacological doses, [11C]cocaine had a higher binding and slower clearance in striatum than in other brain regions. At pharmacological doses, [11C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [11C]cocaine corresponded to 0.5-0.6 and for pharmacological [11C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd' = 3600 nM. Bmax/Kd for sub-pharmacological doses of [11C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [11C]cocaine. CONCLUSION: At subpharmacological doses, [11C]cocaine binds predominantly to a high-affinity site on the dopamine transporter.
UNLABELLED: We have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [11C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. METHODS: PET was used to compare and characterize [11C]cocaine binding in the baboon brain at low subpharmacological (18 micrograms average dose) and at pharmacological (8000 micrograms) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). RESULTS: At subpharmacological doses, [11C]cocaine had a higher binding and slower clearance in striatum than in other brain regions. At pharmacological doses, [11C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [11C]cocaine corresponded to 0.5-0.6 and for pharmacological [11C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd' = 3600 nM. Bmax/Kd for sub-pharmacological doses of [11C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [11C]cocaine. CONCLUSION: At subpharmacological doses, [11C]cocaine binds predominantly to a high-affinity site on the dopamine transporter.
Authors: Najmeh Khalili-Mahani; Serge A R B Rombouts; Matthias J P van Osch; Eugene P Duff; Felix Carbonell; Lisa D Nickerson; Lino Becerra; Albert Dahan; Alan C Evans; Jean-Paul Soucy; Richard Wise; Alex P Zijdenbos; Joop M van Gerven Journal: Hum Brain Mapp Date: 2017-02-01 Impact factor: 5.038
Authors: Nelly Alia-Klein; Muhammad A Parvaz; Patricia A Woicik; Anna B Konova; Thomas Maloney; Elena Shumay; Ruiliang Wang; Frank Telang; Anat Biegon; Gene-Jack Wang; Joanna S Fowler; Dardo Tomasi; Nora D Volkow; Rita Z Goldstein Journal: Arch Gen Psychiatry Date: 2011-03
Authors: D Murali; T E Barnhart; N T Vandehey; B T Christian; R J Nickles; A K Converse; J A Larson; J E Holden; M L Schneider; O T Dejesus Journal: Appl Radiat Isot Date: 2012-10-23 Impact factor: 1.513
Authors: Nora D Volkow; Gene-Jack Wang; Scott H Kollins; Tim L Wigal; Jeffrey H Newcorn; Frank Telang; Joanna S Fowler; Wei Zhu; Jean Logan; Yeming Ma; Kith Pradhan; Christopher Wong; James M Swanson Journal: JAMA Date: 2009-09-09 Impact factor: 56.272