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
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.