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Selective TAAR1 agonists induce conditioned taste aversion
Jianfeng Liu1,2, Ruyan Wu2, Bernard Johnson2
1School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu Province, China.
Psychopharmacology
|September 2, 2022
Summary
Selective trace amine-associated receptor 1 (TAAR1) agonists, proposed for mental disorders, can cause conditioned taste aversion (CTA). This suggests TAAR1 activation may produce aversive effects, requiring careful clinical evaluation.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Trace amine-associated receptor 1 (TAAR1) is implicated in neuropsychiatric disorders.
- TAAR1 agonists show therapeutic potential for schizophrenia and addiction.
- Aversive effects of TAAR1 agonists are largely unknown.
Purpose of the Study:
- To investigate if selective TAAR1 agonists RO5166017 and RO5263397 induce conditioned taste aversion (CTA).
Main Methods:
- Rats were administered selective TAAR1 full agonist RO5166017 and partial agonist RO5263397.
- Conditioned taste aversion (CTA) was assessed using saccharin and NaCl taste novelty.
- Experiments included wild-type, TAAR1 heterozygous knockout (taar1±), and homozygous knockout (taar1-/-) rats.
Main Results:
- Both RO5166017 and RO5263397 induced significant aversions to saccharin and NaCl taste novelty.
- RO5166017 induced CTA in wild-type and taar1± rats, but not in taar1-/- rats.
- TAAR1 activation was sufficient for the taste-aversive properties of RO5166017.
Conclusions:
- Selective TAAR1 agonists can produce robust conditioned taste aversion (CTA).
- These findings highlight the potential aversive effects of TAAR1 agonists.
- Further evaluation of TAAR1 agonist aversive properties is crucial before clinical application.
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