title: Increased context-dependent conditioning to amphetamine in mice lacking TAAR1.
abstract: Given the recent evidence indicating that amphetamine derivatives may also act as direct agonists of the G protein-coupled trace amine-associated receptor 1 (TAAR1), we hypothesized that TAAR1 could contribute to the reinforcing and addictive properties of amphetamines. Accordingly, the present study aimed to investigate the role of TAAR1 in the effects of psychostimulants by analyzing context-dependent sensitization and conditioned place preference (CPP) to d-amphetamine (AMPH) in TAAR1-KO mice. In context-dependent sensitization experiment, TAAR1-KO mice showed higher conditioned locomotor responses compared to wild-type mice. In the CPP test, TAAR1-KO animals were also more sensitive to priming-induced reinstatement of AMPH-induced conditioned place preference (CPP) than wild type mice. Importantly, saline-treated and AMPH-treated mice lacking TAAR1 demonstrated significant alterations in the total levels and phosphorylation of the critical subunit of NMDA glutamate receptors, GluN1, in the striatum, suggesting a role of TAAR1 in the modulation of frontostriatal glutamate transmission; this effect could underlie the observed alterations in conditioning processes. In conclusion, our data suggest that TAAR1 receptors play an inhibitory role with respect to conditioned responses to AMPH by modulating, at least in part, corticostriatal glutamate transmission.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy; St. Petersburg State Medical University, 197022 St. Petersburg, Russia.
authors.forename: Ilya
authors.initials: I
authors.lastname: Sukhanov
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Caffino
authors.affiliation: Skolkovo Institute of Science and Technology, Skolkovo, 143025 Moscow Region, Russia; Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia.
authors.forename: Evgeniya V
authors.initials: EV
authors.lastname: Efimova
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Espinoza
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Sotnikova
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Experimental Psychopharmacology, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cervo
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Skolkovo Institute of Science and Technology, Skolkovo, 143025 Moscow Region, Russia; Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia. Electronic address: raul.gainetdinov@iit.it.
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000095383:Trace Amine-Associated Receptors
chemical_list: D000661:Amphetamine; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D000095383:Trace Amine-Associated Receptors; C121673:Gprin1 protein, mouse
keywords: Amphetamine; Conditioning; NMDA glutamate receptors; Trace amine-associated receptor 1 (TAAR1)