title: Implication of the endocannabinoid system in the locomotor hyperactivity associated with congenital hypothyroidism.
abstract: Alterations in motor functions are well-characterized features observed in humans and experimental animals subjected to thyroid hormone dysfunctions during development. Here we show that congenitally hypothyroid rats display hyperactivity in the adult life. This phenotype was associated with a decreased content of cannabinoid receptor type 1 (CB(1)) mRNA in the striatum and a reduction in the number of binding sites in both striatum and projection areas. These findings suggest that hyperactivity may be the consequence of a thyroid hormone deficiency-induced removal of the endocannabinoid tone, normally acting as a brake for hyperactivity at the basal ganglia. In agreement with the decrease in CB(1) receptor gene expression, a lower cannabinoid response, measured by biochemical, genetic and behavioral parameters, was observed in the hypothyroid animals. Finally, both CB(1) receptor gene expression and the biochemical and behavioral dysfunctions found in the hypothyroid animals were improved after a thyroid hormone replacement treatment. Thus, the present study suggests that impairment in the endocannabinoid system can underlay the hyperactive phenotype associated with hypothyroidism.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense 28040 Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Asúa
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Bilbao
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Gorriti
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Lopez-Moreno
authors.forename: Maria
authors.initials: M
authors.lastname: Del Mar Alvarez
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.forename: Ana
authors.initials: A
authors.lastname: Perez-Castillo
authors.forename: Angel
authors.initials: A
authors.lastname: Santos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003409:Congenital Hypothyroidism / Q000150:complications* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D063388:Endocannabinoids; D005260:Female; D006948:Hyperkinesis / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D014284:Triiodothyronine