title: The CB1 receptor is required for the establishment of the hyperlocomotor phenotype in developmentally-induced hypothyroidism in mice.
abstract: Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R-/-) and in their wild type littermates (CB1R+/+), whose hypothyroidism was induced in day 12 of gestation and maintained during the experimental period. Our results show that hypothyroidism induced a hyperlocomotor phenotype only in CB1R+/+, but not in CB1R-/-mice. In contrast with our previous results in rats, the expression of CB1R in striatum and the motor response to the cannabinoid agonist HU210 was unaltered in hypothyroid CB1R+/+mice suggesting that the cannabinoid system is not altered by hypothyroidism. Also, no effect of HU210 was observed in locomotion of CB1R-/-mice. Finally, since the dopaminergic system plays a major role in the control of locomotor activity we studied its function in hypothyroid wild type and knockout animals. Our results show no alteration in the behavioral response induced by the dopamine D1 receptor agonist SKF38393. However we observed a decreased response to the dopamine D2 receptor antagonist haloperidol only in hypothyroid CB1R+/+mice, which might indicate potential alterations in D2R signaling in these animals. In conclusion, our data suggest that the cannabinoid system is necessary for the induction of hyperlocomotor phenotype in mice with developmentally induced hypothyroidism.
authors.affiliation: Departamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Giné
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Echeverry-Alzate
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Lopez-Moreno
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Spain; Fundación IMABIS, Laboratorio de Medicina Regenerativa, Hospital Regional Universitario Carlos Haya, Malaga, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez de Fonseca
authors.affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas-Universidad Autónoma de Madrid, 28029 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Spain. Electronic address: aperez@iib.uam.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Perez-Castillo
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain. Electronic address: piedras3@med.ucm.es.
authors.forename: Angel
authors.initials: A
authors.lastname: Santos
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007037:Hypothyroidism / Q000378:metabolism*; D007093:Imidazoles; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010472:Perchlorates; D010641:Phenotype; D017680:Potassium Compounds; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: C107674:2-mercapto-1-methylimidazole; C578453:CNR1 protein, mouse; D063386:Cannabinoid Receptor Agonists; C000600618:DRD2 protein, mouse; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C583261:Drd1 protein, mouse; D007093:Imidazoles; D010472:Perchlorates; D017680:Potassium Compounds; D043884:Receptor, Cannabinoid, CB1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C009006:potassium perchlorate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013759:Dronabinol; D006220:Haloperidol; C062018:HU 211
keywords: Cannabinoid receptor type 1; Cannabinoids; Dopamine; Hypothyroidism