Drug addiction is a US public health and safety concern, urging improved treatment approaches such as targeted pharmacotherapies. Preclinical data have provided evidence that dopamine D3 receptor (DRD3) antagonism decreases addiction-relevant behaviour. Buspirone is an FDA-approved anxiolytic which acts as a serotonin partial agonist but has been recently identified as a DRD3 antagonist. Imaging with positron emission tomography (PET) permits the measurement of neurochemicals in vivo. PET has become a powerful tool for neuroscientists to visualize and localize receptors and estimate receptor occupancy by drug ligands. The process of imaging requires the injection of a positron-emitting radiotracer (e.g. [11C]-(+)-PHNO) that binds to the protein of interest (e.g. dopamine D3 receptors) followed by the measurement of this binding using the PET scanner. [11C]-(+)-PHNO is the only ligand allowing to measure dopamine D3 receptors occupancy in humans. Here, we will determine if buspirone significantly occupies the DRD3 at therapeutic doses in humans. These studies will allow for the translation of basic science discoveries into clinical validation. Our long term goal will be to determine the possible use of buspirone as an intervention for tobacco dependence.

Public Health Relevance

Buspirone is an FDA-approved anxiolytic which acts as a serotonin partial agonist but has been recently identified as a dopamine D3 antagonist. Furthermore, recent brain imaging approaches have been developed allowing to measure dopamine D3 receptors in humans. The present project will determine the dose-occupancy relationship of buspirone for the dopamine D3 receptor in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA033515-01
Application #
8283511
Study Section
Special Emphasis Panel (ZRG1-DTCS-U (81))
Program Officer
Grant, Steven J
Project Start
2012-09-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$141,076
Indirect Cost
$10,450
Name
Centre for Addiction and Mental Health
Department
Type
DUNS #
207855271
City
Toronto
State
ON
Country
Canada
Zip Code
M5S2S-1
Le Foll, Bernard; Payer, Doris; Di Ciano, Patricia et al. (2016) Occupancy of Dopamine D3 and D2 Receptors by Buspirone: A [11C]-(+)-PHNO PET Study in Humans. Neuropsychopharmacology 41:529-37
Le Foll, Bernard; Ng, Enoch; Di Ciano, Patricia et al. (2015) Psychiatric disorders as vulnerability factors for nicotine addiction: what have we learned from animal models? Curr Top Behav Neurosci 24:155-70
Boileau, Isabelle; Nakajima, Shinichiro; Payer, Doris (2015) Imaging the D3 dopamine receptor across behavioral and drug addictions: Positron emission tomography studies with [(11)C]-(+)-PHNO. Eur Neuropsychopharmacol 25:1410-20
Le Foll, Bernard; Di Ciano, Patricia (2015) Neuronal circuitry underlying the impact of D3 receptor ligands in drug addiction. Eur Neuropsychopharmacol 25:1401-9
Khaled, Maram A T M; Pushparaj, Abhiram; Di Ciano, Patricia et al. (2014) Dopamine D3 receptors in the basolateral amygdala and the lateral habenula modulate cue-induced reinstatement of nicotine seeking. Neuropsychopharmacology 39:3049-58
Di Ciano, Patricia; Grandy, David K; Le Foll, Bernard (2014) Dopamine D4 receptors in psychostimulant addiction. Adv Pharmacol 69:301-21
Leggio, Gian Marco; Camillieri, Giovanni; Platania, Chiara B M et al. (2014) Dopamine D3 receptor is necessary for ethanol consumption: an approach with buspirone. Neuropsychopharmacology 39:2017-28