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Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors

Authors
 Juan Ji An  ;  Mi-Hyun Bae  ;  Ja-Hyun Baik  ;  Emiliana Borrelli  ;  Kye Won Park  ;  Yong Nyun Kim  ;  Hee-Sup Shin  ;  Bae Hwan Lee  ;  Seong-Hoon Choi  ;  Soo-Hyun Lee  ;  Sang Rae Cho 
Citation
 MOLECULAR AND CELLULAR NEUROSCIENCE, Vol.25(4) : 732-741, 2004 
Journal Title
MOLECULAR AND CELLULAR NEUROSCIENCE
ISSN
 1044-7431 
Issue Date
2004
MeSH
Animals ; Basal Ganglia/drug effects ; Basal Ganglia/metabolism* ; Basal Ganglia/physiopathology ; Brain Chemistry/genetics* ; Dopamine/metabolism ; Electroencephalography/drug effects ; Enkephalins/metabolism ; GABA Agonists/pharmacology ; GABA Antagonists/pharmacology ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; Glutamate Decarboxylase/metabolism ; Male ; Mice ; Mice, Knockout ; Motor Activity/drug effects ; Motor Activity/physiology ; Neural Inhibition/drug effects ; Neural Inhibition/physiology ; Receptors, Dopamine D2/deficiency ; Receptors, Dopamine D2/genetics* ; Receptors, GABA-A/metabolism ; Seizures/chemically induced ; Seizures/enzymology ; Synaptic Transmission/drug effects ; Synaptic Transmission/physiology* ; Up-Regulation/drug effects ; Up-Regulation/physiology ; gamma-Aminobutyric Acid/metabolism*
Abstract
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S1044743103004007
DOI
10.1016/j.mcn.2003.12.010
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Bae Hwan(이배환) ORCID logo https://orcid.org/0000-0003-4719-9021
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111695
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