title: Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors.
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 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.
authors.affiliation: Laboratory of Electrophysiology, Medical Research Center, College of Medicine, Yonsei University, Seoul 120-752, South Korea.
authors.forename: Juan Ji
authors.initials: JJ
authors.lastname: An
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Bae
authors.forename: Sang Rae
authors.initials: SR
authors.lastname: Cho
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Choi
authors.forename: Bae Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Yong Nyun
authors.initials: YN
authors.lastname: Kim
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.forename: Emiliana
authors.initials: E
authors.lastname: Borrelli
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D004745:Enkephalins / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics*; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D004745:Enkephalins; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D004298:Dopamine