Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors

Juan Ji An; Mi Hyun Bae; Sang Rae Cho; Soo Hyun Lee; Seong Hoon Choi; Bae Hwan Lee; Hee Sup Shin; Yong Nyun Kim; Kye Won Park; Emiliana Borrelli; Ja Hyun Baik

doi:10.1016/j.mcn.2003.12.010

Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors

Juan Ji An, Mi Hyun Bae, Sang Rae Cho, Soo Hyun Lee, Seong Hoon Choi, Bae Hwan Lee, Hee Sup Shin, Yong Nyun Kim, Kye Won Park, Emiliana Borrelli, Ja Hyun Baik

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English
Pages (from-to)	732-741
Number of pages	10
Journal	Molecular and Cellular Neuroscience
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.mcn.2003.12.010
State	Published - Apr 2004
Externally published	Yes

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10.1016/j.mcn.2003.12.010

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@article{a5a115866229470aa233dce689b9fa23,

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 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.",

author = "An, \{Juan Ji\} and Bae, \{Mi Hyun\} and Cho, \{Sang Rae\} and Lee, \{Soo Hyun\} and Choi, \{Seong Hoon\} and Lee, \{Bae Hwan\} and Shin, \{Hee Sup\} and Kim, \{Yong Nyun\} and Park, \{Kye Won\} and Emiliana Borrelli and Baik, \{Ja Hyun\}",

year = "2004",

month = apr,

doi = "10.1016/j.mcn.2003.12.010",

language = "English",

volume = "25",

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journal = "Molecular and Cellular Neuroscience",

issn = "1044-7431",

publisher = "Academic Press Inc.",

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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

Y1 - 2004/4

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.

UR - https://www.scopus.com/pages/publications/11144356288

U2 - 10.1016/j.mcn.2003.12.010

DO - 10.1016/j.mcn.2003.12.010

M3 - Article

C2 - 15080900

AN - SCOPUS:11144356288

SN - 1044-7431

VL - 25

SP - 732

EP - 741

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

IS - 4

ER -

Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors

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