title: TAAR1-dependent effects of apomorphine in mice.
abstract: G protein-coupled trace amine-associated receptor 1 (TAAR1) is expressed in several brain regions and modulates dopaminergic activity partially by affecting D2 dopamine receptor function. In vitro, the nonselective dopamine agonist apomorphine can activate mouse and rat TAAR1. The aim of the present study was to evaluate whether apomorphine activity at the rodent TAAR1 observed in in vitro studies contributes to its behavioral manifestation in mice. For this purpose, we compared the behavioral effects of a wide range of apomorphine doses in wild type (WT) and TAAR1 knockout (TAAR1-KO) mice. Apomorphine-induced locomotor responses (0.01-4.0 mg/kg) were tested in locomotor activity boxes, and stereotypic behavior at 5 mg/kg was tested by ethological methods. A gnawing test was used to analyze the effects of the highest dose of apomorphine (10 mg/kg). No statistically significant differences were observed between TAAR1-KO and WT mice following inhibitory pre-synaptic low doses of apomorphine. At higher doses (2.0-5.0 mg/kg), apomorphine-induced climbing behavior was significantly reduced in TAAR1 mutants relative to WT controls. Moreover, the lack of TAAR1 receptors decreased certain types of stereotypies (as reflected in by measures of the global stereotypy score, licking but not sniffing or gnawing) that were induced by high doses of apomorphine. These data indicate that apomorphine activity at TAAR1 contributes to some behavioral manifestations, particularly climbing, in rodents following high doses of this drug. The contribution of TAAR1 to apomorphine-induced climbing in rodents should be considered when apomorphine is used as a screening tool in the search for potential antipsychotics.
authors.affiliation: Department of Neuroscience and Brain Technology,Istituto Italiano di Tecnologia,16163, Genova,Italy.
authors.forename: Ilya
authors.initials: I
authors.lastname: Sukhanov
authors.affiliation: Department of Neuroscience and Brain Technology,Istituto Italiano di Tecnologia,16163, Genova,Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Espinoza
authors.affiliation: Department of Pharmacology,Volgograd State Medical University,400131, Volgograd,Russia.
authors.forename: Dmitriy S
authors.initials: DS
authors.lastname: Yakovlev
authors.affiliation: Neuroscience Research, Pharmaceuticals Division,F. Hoffmann-La Roche Ltd.,CH-4070 Basel,Switzerland.
authors.forename: Marius C
authors.initials: MC
authors.lastname: Hoener
authors.affiliation: Department of Neuroscience and Brain Technology,Istituto Italiano di Tecnologia,16163, Genova,Italy.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Sotnikova
authors.affiliation: Department of Neuroscience and Brain Technology,Istituto Italiano di Tecnologia,16163, Genova,Italy.
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011597:Psychomotor Performance / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000095383:Trace Amine-Associated Receptors
chemical_list: D001058:Apomorphine; D001552:Benzazepines; D000242:Cyclic AMP; D018491:Dopamine Agonists; D010080:Oxazoles; D010627:Phenethylamines; D019257:Quinpirole; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors; C583451:RO5166017; C067113:SK&F 81297