About this item:

189 Views | 168 Downloads

Author Notes:

Heather L. Kimmel, Division of Neuroscience, Yerkes National Primate Research Center, 954 Gatewood Rd. NE, Atlanta, GA 30329, Phone: 404-727-7730, Fax: 404-727-1266, Email: hkimme@emory.edu.

The authors thank Juliet Brown, Paul Chen, and Mi Zhou for their expert technical assistance in conducting this work.

Subjects:

Research Funding:

This research was supported by USPHS grants DA00517 (LLH), DA12514 (LLH), DA13326 (FIC), and DA010344 (LLH); RR00165 (Division of Research Resources, NIH); and Emory University Research Committee grant 281217, Emory University Research Council (URC) (HLK).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • in vivo microdialysis
  • monoamine
  • psychostimulant
  • trafficking
  • transporter
  • POSITRON-EMISSION-TOMOGRAPHY
  • RHESUS-MONKEYS
  • LOCAL-ANESTHETICS
  • IN-VIVO
  • SEROTONIN TRANSPORTER
  • RAPID REGULATION
  • RAT STRIATUM
  • BRAIN
  • INHIBITORS
  • STIMULANT

Simultaneous measurement of extracellular dopamine and dopamine transporter occupancy by cocaine analogs in squirrel monkeys

Tools:

Journal Title:

Synapse

Volume:

Volume 66, Number 6

Publisher:

, Pages 501-508

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Several classes of drugs bind to the dopamine transporter (DAT) with high affinity, but some are weaker positive reinforcers than cocaine, suggesting that affinity for and occupancy of the DAT is not the only determinant of a drug's reinforcing effectiveness. Other factors such as the rate of onset have been positively and strongly correlated with the reinforcing effects of DAT inhibitors in nonhuman primates. In the current studies, we examined the effects of acute systemic administration of cocaine and three cocaine analogs (RTI-150, RTI-177, and RTI-366) on binding to DAT in squirrel monkey brain using positron emission tomography (PET) neuroimaging. During the PET scan, we also measured drug effects on dopamine (DA) levels in the caudate using in vivo microdialysis. In general, our results suggest a lack of concordance between drug occupancy at DAT and changes in DA levels. These studies also indicate that acute cocaine administration decreases the availability of plasma membrane DAT for binding, even after cocaine is no longer blocking DA uptake as evidence by a return to basal DA levels.

Copyright information:

© 2012 Wiley Periodicals, Inc.

Export to EndNote