TY - JOUR
T1 - Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors
AU - An, Juan Ji
AU - Bae, Mi Hyun
AU - Cho, Sang Rae
AU - Lee, Soo Hyun
AU - Choi, Seong Hoon
AU - Lee, Bae Hwan
AU - Shin, Hee Sup
AU - Kim, Yong Nyun
AU - Park, Kye Won
AU - Borrelli, Emiliana
AU - Baik, Ja Hyun
PY - 2004/4/1
Y1 - 2004/4/1
N2 - 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 GABAA 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 GABAA-receptor mediated signaling, and stimulating the GABAA receptor can reverse the dysfunction of GABAergic inhibition in the motor circuits in the basal ganglia.
AB - 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 GABAA 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 GABAA-receptor mediated signaling, and stimulating the GABAA receptor can reverse the dysfunction of GABAergic inhibition in the motor circuits in the basal ganglia.
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U2 - 10.1016/j.mcn.2003.12.010
DO - 10.1016/j.mcn.2003.12.010
M3 - Article
C2 - 15080900
AN - SCOPUS:11144356288
VL - 25
SP - 732
EP - 741
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 4
ER -