Dopamine Rhythms in Health and Addiction

Summary

Background: \- Dopamine is a chemical signal linked to the rewarding effects of drugs. Certain genes make these effects sensitive to the time of day they are taken. Cocaine can affect these genes in the brain. Researchers want to measure brain dopamine at different times of day. Objectives: \- To look for changes to a person s biological clock in the function of the dopamine reward system. To test if cocaine disrupts this. Eligibility: * Adults age 21-55 with a cocaine use disorder. * Healthy volunteers age 21-55. Design: * Participants will be screened with medical history, physical exam, interview, and blood and urine tests. Their breath will be tested for alcohol and recent smoking. * Participants will have 3 overnight clinic visits. * Visit 1: They will have blood and urine collected and a heart test. * A plastic tube (catheter) will be placed into a vein in each arm by needle. * Participants will have a PET scan in a donut-shaped machine. They will lie on a bed that slides in and out of it, wearing a cap. A radiotracer (measures dopamine) and a drug (blocks dopamine removal) will be injected via catheter. Vital signs will be measured and blood will be drawn throughout. * Visit 2: repeats Visit 1, except at night. * Visit 3, participants will have urine collected. * They will have MRI scans in a metal cylinder surrounded by a magnetic field. They will lie on a table that slides in and out of it, with a coil over their head. * Participants may answer questions, take computer or paper tests, and perform simple actions. * For 1 week, participants will wear a wrist device that measures daily activity.

Timeline

Start

2024-04-23

Primary completion

2024-04-23

Completion

2024-04-23

Publications

• Background Wang GJ, Volkow ND, Fowler JS, Logan J, Pappas NR, Wong CT, Hitzemann RJ, Netusil N. Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. J Nucl Med. 1999 Aug;40(8):1285-91.
• Background Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS. Brain dopamine and obesity. Lancet. 2001 Feb 3;357(9253):354-7. doi: 10.1016/s0140-6736(00)03643-6.
• Background Dunn JP, Cowan RL, Volkow ND, Feurer ID, Li R, Williams DB, Kessler RM, Abumrad NN. Decreased dopamine type 2 receptor availability after bariatric surgery: preliminary findings. Brain Res. 2010 Sep 2;1350:123-30. doi: 10.1016/j.brainres.2010.03.064. Epub 2010 Mar 31.

Drugs

Indications