Primate trace amine receptor 1 modulation by the dopamine transporter.

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Trace amine receptors (TARs) are emerging targets for psychoactive substances.
• Amphetamine and MDMA are drugs of abuse with known interactions with monoamine transporters.

Purpose of the Study:

• To clone and characterize the rhesus monkey trace amine receptor 1 (rhTA(1)).
• To investigate the direct and indirect effects of drugs of abuse on rhTA(1) activity.
• To assess the potential of nonhuman primates as models for human TA(1) research.

Main Methods:

• Cloning of full-length rhTA(1).
• cAMP accumulation assays in rhTA(1)-expressing cell lines using a luciferase reporter.
• [(3)H]PEA transport assays to measure dopamine transporter function.
• Cotransfection experiments with human dopamine transporter.

Main Results:

• rhTA(1) shares 96% homology with human TA(1).
• Trace amines (tyramine, PEA) and drugs (amphetamine, MDMA) stimulated cAMP accumulation in rhTA(1) cells.
• Cocaine inhibited [(3)H]PEA transport but did not activate rhTA(1).
• Dopamine transporter presence modulated rhTA(1) activation by different agonists.

Conclusions:

• Primate TA(1) receptors are direct targets for trace amines, amphetamine, and MDMA.
• These receptors may also be indirect targets through modulation of monoamine transporter function.
• rhTA(1) may be colocalized with dopamine transporters in primate substantia nigra.
• Nonhuman primates offer a valuable model for studying TA(1)-mediated responses relevant to humans.