Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors.
Mol Cell Neurosci
; 25(4): 732-41, 2004 Apr.
Article
en En
| MEDLINE
| ID: mdl-15080900
The levels of glutamic acid decarboxylase (GAD) were strongly increased in the cortex and the striatum in dopamine D2 receptors null (D2R-/-) mice, which show a significant locomotor impairment. In this study, the effects of different GABAergic drugs on locomotor activity were analyzed in D2R-/- mice. After administering muscimol (1 mg/kg), a GABA(A) receptor agonist, the D2R-/- mice showed increased locomotor activity up to 200%. When the muscimol dose was increased (4-6 mg/kg), the D2R-/- mice exhibited seizure-like behavior, and the electroencephalographic (EEG) recordings during these behaviors showed a high amplitude rhythmic epileptiform activity in these mice. In situ hybridization showed that after injecting muscimol in the D2R-/- mice, the expression of enkephalin and immediate early gene, NGFI-A, was closely regulated with the locomotor activity regulated by GABAergic stimulation. These results suggest that the absence of D2R alters the GABAergic neurotransmission, specifically on GABA(A)-receptor mediated signaling, and stimulating the GABA(A) receptor can reverse the dysfunction of GABAergic inhibition in the motor circuits in the basal ganglia.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ganglios Basales
/
Química Encefálica
/
Receptores de Dopamina D2
/
Transmisión Sináptica
/
Ácido gamma-Aminobutírico
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Neurosci
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Corea del Sur
Pais de publicación:
Estados Unidos