Asúa, TeresaBilbao, AinhoaGorriti, Miguel AngelLopez-Moreno, Jose AntonioAlvarez, Maria del MarNavarro, MiguelRodríguez de Fonseca, FernandoPerez-Castillo, AnaSantos, Angel2012-12-032012-12-032008-05Asúa T, Bilbao A, Gorriti MA, Lopez-Moreno JA, Alvarez MM, Navarro M, et al. Implication of the endocannabinoid system in the locomotor hyperactivity associated with congenital hypothyroidism. Endocrinology. 2008 May; 149(5):2657-660013-7227http://hdl.handle.net/10668/679Journal Article; Research Support, Non-U.S. Gov't;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.enAnimalesAnimales recién nacidosGanglios basalesConducta animalCerebeloHipotiroidismo congénitoEvaluación preclínica de medicamentosEndocannabinoidesFemeninoHipercinesiaActividad MotoraEmbarazoARN mensajeroRatasRatas WistarReceptor cannabinoide CB1TriyodotironinaMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, NewbornMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Basal GangliaMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavior, AnimalMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Rhombencephalon::Metencephalon::CerebellumMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Dwarfism::Congenital HypothyroidismMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, PreclinicalMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::EndocannabinoidsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Dyskinesias::HyperkinesisMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor ActivityMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::PregnancyMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, WistarMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Thyroid Hormones::Thyronines::TriiodothyronineMedical Subject Headings::Organisms::Eukaryota::Animalsresearch article18218697open access10.1210/en.2007-15861945-7170