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| ID | Type | Description | Link |
|---|---|---|---|
| R21DA031925-01A1 | U.S. NIH Grant/Contract | View source |
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Technical complications.
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
This trial aims to determine whether dopamine D3 receptors are elevated in smokers versus nonsmokers and whether correlations exist between D3 receptor binding potential (BP) and functional MRI (fMRI) reactivity to smoking cues, which has been associated with smoking relapse vulnerability.
Neuroimaging measures of D3 BP and smoking cue fMRI reactivity will be collected concurrently in otherwise healthy nicotine-dependent smokers and age-matched nonsmokers using a 3 Tesla MRI scanner configured to conduct fMRI and Positron Emission Tomography (PET).
We will measure D3 receptor BP using radiolabeled [11C]-(+)-PHNO, which has a relatively higher affinity for D3 versus D2 receptors.
We hypothesize that D3 BP will be elevated in smokers versus nonsmokers and that in smokers, there will be a positive correlation between smoking cue fMRI reactivity and D3 BP.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Smokers | Experimental | Healthy smokers aged 18-50 years reporting average cigarette consumption of 15 or more cigarettes/day for the past year, providing an expired breath carbon monoxide reading exceeding 10 ppm at screening. |
|
| Healthy Nonsmokers | Experimental | Healthy nonsmoking controls aged 18-50 reporting consumption of <100 cigarettes in their lifetime, none in the last 6 months, providing an exhaled breath carbon monoxide reading of < 9 ppm at screening. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [11C]-PHNO | Radiation | [11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers | We will determine whether dopamine D3 receptor binding potential, a dimensionless number which represents the relative concentration of dopamine D3 receptors available for binding, is elevated in smokers versus nonsmoking controls. | March 2014 |
| Measure | Description | Time Frame |
|---|---|---|
| Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential | In smokers, we will determine whether an association exists between smoking cue fMRI reactivity intensity (beta weight) and dopamine D3 receptor binding potential, a relationship between receptor (D3) density and dopamine occupancy. | March 2014 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc J. Kaufman, Ph.D. | Mclean Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McLean Hospital | Belmont | Massachusetts | 02478 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20172508 | Background | Janes AC, Pizzagalli DA, Richardt S, deB Frederick B, Chuzi S, Pachas G, Culhane MA, Holmes AJ, Fava M, Evins AE, Kaufman MJ. Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biol Psychiatry. 2010 Apr 15;67(8):722-9. doi: 10.1016/j.biopsych.2009.12.034. Epub 2010 Feb 20. | |
| 12494400 | Background | Le Foll B, Diaz J, Sokoloff P. Increased dopamine D3 receptor expression accompanying behavioral sensitization to nicotine in rats. Synapse. 2003 Mar;47(3):176-83. doi: 10.1002/syn.10170. |
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| ID | Term |
|---|---|
| D014029 | Tobacco Use Disorder |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C042631 | naxagolide |
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|
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging | Charlestown | Massachusetts | 02129 | United States |
| 20599188 | Background | Searle G, Beaver JD, Comley RA, Bani M, Tziortzi A, Slifstein M, Mugnaini M, Griffante C, Wilson AA, Merlo-Pich E, Houle S, Gunn R, Rabiner EA, Laruelle M. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist. Biol Psychiatry. 2010 Aug 15;68(4):392-9. doi: 10.1016/j.biopsych.2010.04.038. |
| 20600980 | Background | Tziortzi AC, Searle GE, Tzimopoulou S, Salinas C, Beaver JD, Jenkinson M, Laruelle M, Rabiner EA, Gunn RN. Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage. 2011 Jan 1;54(1):264-77. doi: 10.1016/j.neuroimage.2010.06.044. Epub 2010 Jun 30. |
| 15943487 | Background | Wilson AA, McCormick P, Kapur S, Willeit M, Garcia A, Hussey D, Houle S, Seeman P, Ginovart N. Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. J Med Chem. 2005 Jun 16;48(12):4153-60. doi: 10.1021/jm050155n. |
| 16942635 | Background | Pak AC, Ashby CR Jr, Heidbreder CA, Pilla M, Gilbert J, Xi ZX, Gardner EL. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions. Int J Neuropsychopharmacol. 2006 Oct;9(5):585-602. doi: 10.1017/S1461145706006560. Epub 2006 Aug 31. |