Activation of TAAR1 attenuates extended access of cocaine self‐administration and stress‐induced reinstatement of cocaine‐seeking

Abstract

Trace amine‐associated receptor 1 (TAAR1) is the best‐characterized sub‐family of receptors of trace amines. As a modulator of dopaminergic system, TAAR1 has been shown to play a critical role in regulating the rewarding properties of drugs of abuse such as cocaine. In our previous studies, we demonstrated that TAAR1 agonists were able to reduce cocaine intake and cue‐ and drug‐induced reinstatements of cocaine‐seeking under short‐access conditions. However, compared to the extended access of cocaine self‐administration model, the short‐access model could not mimic some core properties of addiction, such as escalation, compulsive motivation, and incubation of cocaine‐seeking. Furthermore, it remains unclear whether activation of TAAR1 would affect stress‐induced reinstatement of cocaine‐seeking. Here, we investigated the effects of TAAR1 partial agonist RO5263397 on the extended access of cocaine self‐administration. We also assessed the effects of the selective TAAR1 full agonist RO5166017 on the yohimbine‐induced reinstatement of cocaine‐seeking. We found that the TAAR1 partial agonist RO5263397 attenuated the escalation, break point, and cue‐seeking behavior in the extended access of cocaine self‐administration model. We also found that RO5166017 reduced yohimbine‐induced reinstatement of cocaine‐seeking and yohimbine‐potentiated cue‐induced reinstatement of cocaine seeking, indicating that activation of TAAR1 decreased the stress‐induced reinstatement of cocaine‐seeking. Taken together, our results suggest that TAAR1 is a promising therapeutic target for the treatment of cocaine addiction.Support or Funding InformationThis work was supported by the National Institute of Health Grants R21‐DA033426.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.