This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator.
AIMS : Monoamine transporters regulate neurotransmitter levels, which release or sequester them from and into neurons. Cocaine and other psychostimulants inhibit the dopamine (DAT) and norepinephrine (NET) transporters, with relative potencies that correlate with their potencies for producing stimulant effects and abuse liability. The trace amine phenylethylamine (PEA) is implicated in addiction, but the relationship between PEA, monoamine transporters and drugs is unknown. We postulated that PEA is a substrate for the DAT and NET, that drugs would potently inhibit [3H]PEA transport and that blockade of (3H)PEA transport by DAT inhibitors would be relevant to the stimulant and reinforcing properties of cocaine-like drugs. METHODS: We measured (3H)PEA transport kinetics, compared drug effects on (3H)PEA and (3H)dopamine transport in human DAT-HEK-293 cells, and compared relative drug potencies in vitro with reported drug potencies for producing behavioral effects in primates. RESULTS: (3H)PEA was actively transported, with DAT and NET affinities similar to (3H)dopamine or (3H)norepinephrine affinities. (-)-Cocaine and other drugs dose-dependently inhibited PEA transport by the DAT, at greater potencies than those that block (3H)dopamine transport. The relative potencies of drugs for blocking (3H)PEA transport correlated highly with their reported relative potencies for producing psychomotor stimulation and maintaining self-administration in primates. CONCLUSIONS: Drug inhibition of PEA transport by the DAT and NET conceivably elevates extracellular PEA levels in brain. These results implicate PEA and the trace amine receptor1 activation as contributors to the psychostimulant and reinforcing effects of DAT inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-49
Application #
8172879
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2010-05-01
Project End
2011-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
49
Fiscal Year
2010
Total Cost
$18,052
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519
Arcaro, Michael J; Livingstone, Margaret S (2017) A hierarchical, retinotopic proto-organization of the primate visual system at birth. Elife 6:
McLean, Will J; Yin, Xiaolei; Lu, Lin et al. (2017) Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells. Cell Rep 18:1917-1929

Showing the most recent 10 out of 365 publications