GABAergic Control of Nigrostriatal and Mesolimbic Dopamine in the Rat Brain

GABAergic Control of Nigrostriatal and Mesolimbic Dopamine in the Rat Brain

The present study assessed the effects of the GABA receptor (R) agonist muscimol (MUS), and the GABA R antagonist bicuculline (BIC) on neocortical and subcortical radioligand binding to dopamine D Rs in relation to motor and exploratory behaviors in the rat. D R binding was measured with small anima...

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Published in:Frontiers in behavioral neuroscience Vol. 12; p. 38
Main Authors: Nikolaus, Susanne, Wittsack, Hans-Jörg, Beu, Markus, Antke, Christina, De Souza Silva, Maria A, Wickrath, Frijthof, Müller-Lutz, Anja, Huston, Joseph P, Antoch, Gerald, Müller, Hans-Wilhelm, Hautzel, Hubertus
Format: Journal Article
Language:English
Published: Switzerland Frontiers Research Foundation 14-03-2018
Frontiers Media S.A
Subjects:
[123I]IBZM
Anxiety
Bicuculline
Binding sites
Cerebellum
D2/3 receptor
Dopamine
Dopamine D2 receptors
GABAA receptor
Grooming
Magnetic resonance imaging
Mental disorders
Mesolimbic system
Morphology
Muscimol
Neocortex
Neuroscience
Nucleus accumbens
Rodents
Schizophrenia
Single photon emission computed tomography
Thalamus
Ventral tegmentum
γ-Aminobutyric acid A receptors
Germany
[123I]IBZM
D2/3 receptor
muscimol
GABAA receptor
bicuculline
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Summary:The present study assessed the effects of the GABA receptor (R) agonist muscimol (MUS), and the GABA R antagonist bicuculline (BIC) on neocortical and subcortical radioligand binding to dopamine D Rs in relation to motor and exploratory behaviors in the rat. D R binding was measured with small animal SPECT in baseline and after challenge with either 1 mg/kg MUS or 1 mg/kg BIC, using [ I]IBZM as radioligand. Motor/exploratory behaviors were assessed for 30 min in an open field prior to radioligand administration. Anatomical information was gained with a dedicated small animal MRI tomograph. Based on the Paxinos rat brain atlas, regions of interest were defined on SPECT-MRI overlays. Estimations of the binding potentials in baseline and after challenges were obtained by computing ratios of the specifically bound compartments to the cerebellar reference region. After MUS, D R binding was significantly reduced in caudateputamen, nucleus accumbens, thalamus, substania nigra/ventral tegmental area, and posterior hippocampus relative to baseline (0.005 ≤ ≤ 0.012). In all these areas, except for the thalamus, D R binding was negatively correlated with grooming in the first half and positively correlated with various motor/exploratory behaviors in the second half of the testing session. After BIC, D R binding was significantly elevated in caudateputamen ( = 0.022) and thalamus ( = 0.047) relative to baseline. D R binding in caudateputamen and thalamus was correlated negatively with sitting duration and sitting frequency and positively with motor/exploratory behaviors in the first half of the testing time. Findings indicate direct GABAergic control over nigrostriatal and mesolimbic dopamine levels in relation to behavioral action. This may be of relevance for neuropsychiatric conditions such as anxiety disorder and schizophrenia, which are characterized by both dopaminergic and GABAergic dysfunction.
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Edited by: Liana Fattore, Consiglio Nazionale Delle Ricerche (CNR), Italy
Reviewed by: Tetsuo Yamamori, RIKEN Brain Science Institute (BSI), Japan; Fabrizio Sanna, Università degli Studi di Cagliari, Italy
ISSN:1662-5153
1662-5153
DOI:10.3389/fnbeh.2018.00038