Jianfeng Liu1, Bernard Johnson1, Ruyan Wu1,2, Robert Seaman1, Jimmy Vu1, Qing Zhu3, Yanan Zhang4, Jun-Xu Li1. 1. Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA. 2. School of Medicine, Yangzhou University, Yangzhou, China. 3. School of Pharmacy, Nantong University, Nantong, China. 4. Research Triangle Institute, Research Triangle Park, North Carolina, USA.
Abstract
BACKGROUND AND PURPOSE: The trace amine-associated receptor 1 (TAAR1) negatively modulates dopamine transmission. Our previous studies demonstrated that TAAR1 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 TAAR1 in compulsive cocaine use, we evaluated the effects of activation of TAAR1 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 TAAR1 in stress-triggered cocaine relapse by using the α2 -adrenoceptor antagonist yohimbine-induced reinstatement of cocaine-seeking. KEY RESULTS: The selective TAAR1 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 TAAR1 full agonist RO5166017 reduced yohimbine-induced reinstatement of cocaine-seeking behaviour. CONCLUSION AND IMPLICATIONS: Activation of TAAR1 attenuated extended-access cocaine self-administration and stress-induced cocaine reinstatement. These results suggest that TAAR1 agonists are promising pharmacological interventions to treat cocaine use disorder and relapse.
BACKGROUND AND PURPOSE: The trace amine-associated receptor 1 (TAAR1) negatively modulates dopamine transmission. Our previous studies demonstrated that TAAR1 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 TAAR1 in compulsive cocaine use, we evaluated the effects of activation of TAAR1 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 TAAR1 in stress-triggered cocaine relapse by using the α2 -adrenoceptor antagonist yohimbine-induced reinstatement of cocaine-seeking. KEY RESULTS: The selective TAAR1 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 TAAR1 full agonist RO5166017 reduced yohimbine-induced reinstatement of cocaine-seeking behaviour. CONCLUSION AND IMPLICATIONS: Activation of TAAR1 attenuated extended-access cocaine self-administration and stress-induced cocaine reinstatement. These results suggest that TAAR1 agonists are promising pharmacological interventions to treat cocaine use disorder and relapse.
Authors: B Borowsky; N Adham; K A Jones; R Raddatz; R Artymyshyn; K L Ogozalek; M M Durkin; P P Lakhlani; J A Bonini; S Pathirana; N Boyle; X Pu; E Kouranova; H Lichtblau; F Y Ochoa; T A Branchek; C Gerald Journal: Proc Natl Acad Sci U S A Date: 2001-07-17 Impact factor: 11.205
Authors: Florent G Revel; Claas A Meyer; Amyaouch Bradaia; Karine Jeanneau; Eleonora Calcagno; Cédric B André; Markus Haenggi; Marie-Thérèse Miss; Guido Galley; Roger D Norcross; Roberto W Invernizzi; Joseph G Wettstein; Jean-Luc Moreau; Marius C Hoener Journal: Neuropsychopharmacology Date: 2012-07-04 Impact factor: 7.853