Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

descriptionPublicationkeyboard_double_arrow_right Article 24 Jan 2008 Spain English Publisher:The Endocrine SocietyJournal:Endocrinology, volume 149, pages 2,657-2,666 (issn: 0013-7227, eissn: 1945-7170,

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Authors: Asúa, Teresa; Bilbao, Ainhoa; Gorriti, Miguel Angel; Lopez-Moreno, Jose Antonio; Alvarez, Maria del Mar; Navarro, Miguel; Rodríguez de Fonseca, Fernando; +2 Authors

doi: 10.1210/en.2007-1586

pmid: 18218697

handle: 10261/25040 , 10668/679

Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

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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 (CB1) 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 CB1 receptor gene expression, a lower cannabinoid response, measured by biochemical, genetic and behavioral parameters, was observed in the hypothyroid animals. Finally, both CB1 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.

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Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Dyskinesias::Hyperkinesis, Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy, Drug Evaluation, Preclinical, Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Newborn, Hyperkinesis, Motor Activity, Basal Ganglia, Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity, Receptor, Cannabinoid, CB1, Pregnancy, Cerebellum, Cannabinoid Receptor Modulators, Congenital Hypothyroidism, Animals, Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavior, Animal, RNA, Messenger, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar, Rats, Wistar, Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Rhombencephalon::Metencephalon::Cerebellum, Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Thyroid Hormones::Thyronines::Triiodothyronine, Behavior, Animal, Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids, Medical Subject Headings::Check Tags::Female, Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1, Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Basal Ganglia, Rats, Medical Subject Headings::Organisms::Eukaryota::Animals, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, Preclinical, Medical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Dwarfism::Congenital Hypothyroidism, Animals, Newborn, Triiodothyronine, Female, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats, Endocannabinoids

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