Selective TAAR1 agonists induce conditioned taste aversion

Rationale Trace amine-associated receptor 1 (TAAR1) is the best-studied receptor of trace amines, a group of biogenic amines expressed at a relatively low level in the mammalian brain. Growing evidence suggests that TAAR1 plays a critical role in various neuropsychiatric disorders. Given that selective TAAR1 agonists were shown to produce pro-cognition and antipsychotic-like effects as well as to suppress drug use and relapse, they have been proposed to be novel treatments for mental disorders such as schizophrenia and addiction. However, the aversive effects of selective TAAR1 agonists remain largely unknown. Objectives Here, we evaluated whether the selective TAAR1 full agonist RO5166017 and partial agonist RO5263397 could induce conditioned taste aversion (CTA). Results We found that RO5166017 and RO5263397 produced significant aversions to both saccharin and NaCl taste novelty. Furthermore, RO5166017 produced CTA to saccharin in TAAR1 heterozygous knockout ( taar1 ± ) and wild-type rats but not in TAAR1 homozygous knockout rats ( taar1 −/− ), suggesting that TAAR1 was sufficient for the taste aversive stimulus property of RO5166017. Conclusions Taken together, our data indicate that selective TAAR1 agonists could produce strong CTA. Our study urges careful evaluations of the aversive effects of TAAR1 agonists before translating them to clinical use for the treatment of mental disorders.