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PMID:15080900
| Citation |
An, JJ, Bae, MH, Cho, SR, Lee, SH, Choi, SH, Lee, BH, Shin, HS, Kim, YN, Park, KW, Borrelli, E and Baik, JH (2004) Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors. Mol. Cell. Neurosci. 25:732-41 |
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| 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. |
| Links |
PubMed Online version:10.1016/j.mcn.2003.12.010 |
| Keywords |
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 |
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Significance
Annotations
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