Implication of the endocannabinoid system in the locomotor hyperactivity associated with congenital hypothyroidism.
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.
Asúa
Teresa
T
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense 28040 Madrid, Spain.
Bilbao
Ainhoa
A
Gorriti
Miguel Angel
MA
Lopez-Moreno
Jose Antonio
JA
Del Mar Alvarez
Maria
M
Navarro
Miguel
M
Rodríguez de Fonseca
Fernando
F
Perez-Castillo
Ana
A
Santos
Angel
A
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
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D014284:Triiodothyronine