Researchers have found that a recently discovered signaling system in the brain is turned on by methamphetamine. Oregon Health & Science University (OHSU) scientists demonstrated the new target of meth and amphetamine is a G protein-coupled receptor known as trace amine-associated receptor 1 (TAAR1).
TAAR1 was originally discovered in the laboratory of David K. Grandy, Ph.D., OHSU professor of physiology and pharmacology. Dr. Grandy’s lab found that TAAR1 is activated by chemical relatives of meth known as phenylethylamines. The mRNA that codes for TAAR1 is expressed throughout the brain, including areas involved in motivation, drug craving, olfaction, and temperature regulation.
"With this kind of pharmacological profile and brain distribution, we hypothesized TAAR1 could mediate some of meth’s metabolic and behavioral effects," explains Dr. Grandy, who directed the research. "In our most recent article, we provide clear evidence that methamphetamine is a full and potent agonist of TAAR1."
Dr. Grandy's team explored the effects of these drugs on mouse TAAR1 and a human-rat TAAR1 hybrid and found all of the receptors respond in similar ways.
"The results of this study unequivocally demonstrate that meth and amphetamine are able to directly activate this receptor in the laboratory, making it likely that TAAR1 is activated in chronic users of meth," the researchers state in their article.
Currently, Dr. Grandy is collaborating with Thomas Scanlan, Ph.D., director of the program in chemical biology. Dr. Scanlan’s laboratory has synthesized more than 150 new compounds that are being analyzed for their ability to selectively interfere with TAAR1 and block its activity.
This study is published in the April edition of Pharmacology and Experimental Therapeutics.