Jianfeng Liu1,2, Ruyan Wu2, Bernard Johnson2, Yanan Zhang3, Qing Zhu1, Jun-Xu Li4. 1. School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu Province, China. 2. Department of Pharmacology and Toxicology, Program in Neuroscience, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY, 14203, USA. 3. Research Triangle Institute, Research Triangle Park, NC, 27709, USA. 4. Department of Pharmacology and Toxicology, Program in Neuroscience, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY, 14203, USA. junxuli@buffalo.edu.
Abstract
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.
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.
Authors: J R Bunzow; M S Sonders; S Arttamangkul; L M Harrison; G Zhang; D I Quigley; T Darland; K L Suchland; S Pasumamula; J L Kennedy; S B Olson; R E Magenis; S G Amara; D K Grandy Journal: Mol Pharmacol Date: 2001-12 Impact factor: 4.436
Authors: Jonathan K Gore-Langton; Shaun M Flax; Rebecca L Pomfrey; B Bradley Wetzell; Anthony L Riley Journal: Pharmacol Biochem Behav Date: 2015-05-09 Impact factor: 3.533