TA<sub>1</sub> agonists attenuate extended‐access cocaine self‐administration and yohimbine‐induced reinstatement of cocaine‐seeking
Jianfeng Liu, Bernard Johnson, Ruyan Wu, Robert W. Seaman, Jimmy Vu, Qing Zhu, Yanan Zhang, Jun‐Xu Li
Abstract
Background and Purpose The trace amine‐associated receptor 1 (TA 1 ) negatively modulates dopamine transmission. Our previous studies demonstrated that TA 1 agonists attenuated cue‐ and drug‐induced cocaine‐seeking and increased the elasticity of the cocaine demand curve, in the short‐access cocaine self‐administration model. Compulsive use of cocaine, which is an essential criterion of cocaine use disorder, can be induced by extended access to cocaine self‐administration. Experimental Approach To characterize the role of TA 1 in compulsive cocaine use, we evaluated the effects of activation of TA 1 on cocaine intake, cocaine binge and cue‐induced cocaine‐seeking using the extended‐access cocaine self‐administration model in adult male Sprague–Dawley rats. We also investigated the role of TA 1 in stress‐triggered cocaine relapse by using the α 2 ‐adrenoceptor antagonist yohimbine‐induced reinstatement of cocaine‐seeking. Key Results The selective TA 1 partial agonist RO5263397 attenuated cocaine intake and did not develop tolerance during the 10‐day extended‐access cocaine self‐administration. RO5263397 reduced a 12‐h binge intake of cocaine after forced abstinence. RO5263397 also decreased cue‐induced cocaine‐seeking after prolonged abstinence from extended‐access cocaine self‐administration. Furthermore, RO5263397 and the selective TA 1 full agonist RO5166017 reduced yohimbine‐induced reinstatement of cocaine‐seeking behaviour. Conclusion and Implications Activation of TA 1 attenuated extended‐access cocaine self‐administration and stress‐induced cocaine reinstatement. These results suggest that TA 1 agonists are promising pharmacological interventions to treat cocaine use disorder and relapse.