effect of unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway on GABAA receptor subunit gene expression in the rodent basal ganglia and thalamus

Chadha, Ambika; Dawson, L G; Jenner, Peter; Duty, Susan

doi:10.1016/s0306-4522(99)00413-3

Cited by 52 publications

(27 citation statements)

References 34 publications

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“…Our study also confirms previous findings showing that mRNA levels of the α1 subunit of the GABA A receptor are increased in the SNr ipsilateral to the 6-OHDA lesion (Chadha et al, 2000;Katz et al, 2005). Because striatonigral neurons provide the most prominent GABA input to the SNr/EP (Smith et al, 1998) and that vGAT gene expression is decreased in these neurons (Wang et al, 2007), it is possible that the 6-OHDA-induced up-regulation of GABA A receptors in the SNr/EP is secondary to a decrease in GABA release from striatonigral neurons.…”

Section: Effects Of Unilateral 6-ohda Lesions On Striatal Gaba Neuronssupporting

confidence: 81%

Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABAA receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion

Yamamoto

Soghomonian

2008

Neuroscience

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Striatal projection neurons use GABA as their neurotransmitter and express the rate-limiting synthesizing enzyme glutamic acid decarboxylase (GAD) and the vesicular GABA transporter vGAT. The chronic systemic administration of an agonist of dopamine D1/D5-preferring receptors is known to alter GAD mRNA levels in striatonigral neurons in intact and dopamine-depleted rats. In the present study, the effects of a single or subchronic systemic administration of the dopamine D1/D5-preferring receptor agonist SKF-81297 on GAD65, GAD67, PPD and vGAT mRNA levels in the striatum and GABA A receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, were measured in rats with a unilateral 6-OHDA lesion. After a single injection of SKF-81297, striatal GAD65 mRNA levels were significantly increased at 3 but not 72 hours. In contrast, striatal GAD67 mRNA levels were increased and nigral α1 mRNA levels were decreased at 72 but not 3 hours. Single cell analysis on double-labeled sections indicated that increased GAD or vGAT mRNA levels after acute SKF-81297 occurred in striatonigral neurons identified by their lack of preproenkephalin expression. Subchronic SKF-81297 induced significant increases in striatal GAD67, GAD65, preprodynorphin and vGAT mRNA levels and decreases in nigral α1 mRNA levels. In the striatum contralateral to the 6-OHDA lesion, subchronic but not acute SKF-81297 induced a significant increase in GAD65 mRNA levels. The other mRNA levels were not significantly altered. Finally, striatal GAD67 mRNA levels were negatively correlated with nigral α1 mRNA levels in the dopamine-depleted but not dopamine-intact side. The results suggest that different signaling pathways are involved in the modulation by dopamine D1/D5 receptors of GAD65 and GAD67 mRNA levels in striatonigral neurons. They also suggest that the down-regulation of nigral GABA A receptors is linked to the increase in striatal GAD67 mRNA levels in the dopamine-depleted striatum.

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Section: Effects Of Unilateral 6-ohda Lesions On Striatal Gaba Neuronssupporting

confidence: 81%

Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABAA receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion

Yamamoto

Soghomonian

2008

Neuroscience

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“…In contrast to the influences of 6-OHDA lesion or eticlopride administration, the impact of the STN lesion on pallidal GAD 67 mRNA expression was greater for the PVϩ than PVϪ neurons Pallidal GAD 67 mRNA after nigrostriatal lesion or repeated D2 antagonist: functional implications In the basal ganglia, changes in GAD 67 mRNA expression correlate with increased GAD protein levels, electrophysiological activity, and compensatory downregulation of GABA receptors (Segovia et al, 1990(Segovia et al, , 1991Chada et al, 2000). In other systems (e.g., cerebellum and hippocampus), changes in GAD 67 mRNA expression correlate with increased GAD protein in terminals, increased GABA release, and increases in firing rates of GABAergic neurons (Litwak et al, 1990;Drengler and Oltmans, 1993;Falkenberg et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Glutamic Acid Decarboxylase 67 mRNA Regulation in Two Globus Pallidus Neuron Populations by Dopamine and the Subthalamic Nucleus

Billings¹,

Marshall²

2004

J. Neurosci.

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“…Animals (Scientific Procedures) Act, 1986 and all efforts were made to minimise animals' suffering and the number of animals used. Unilateral 6-OHDA lesions of the nigrostriatal tract were produced as described previously (Chadha et al, 2000). At 30min prior to surgery, rats were injected with pargyline (5 mg kg…”

Section: Methodsmentioning

confidence: 99%

Locomotor effects of imidazoline I₂‐site‐specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6‐hydroxydopamine lesion of the nigrostriatal pathway

MacInnes

Duty

2004

British J Pharmacology

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1 The present study examined the ability of the selective imidazoline I 2 -site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway. 2 Male Sprague-Dawley rats were injected with 12.5 mg 6-hydroxydopamine (6-OHDA) into the right median forebrain bundle to induce a unilateral lesion of the nigrostriatal tract. After 6 weeks, test drugs were administered either alone or in combination with L-DOPA (L-3,4-dihydroxyphenylamine) and the circling behaviour of animals was monitored as an index of anti-Parkinsonian activity. ) significantly increased either the duration or total number of contraversive rotations emitted over the testing period in comparison to L-DOPA alone. 5 These data suggest that I 2 -specific ligands have dual effects in the 6-OHDA-lesioned rat model of Parkinson's disease; a first effect associated with an increase in activity in the intact hemisphere, probably via an increase in striatal dopamine content, and a secondary action which, through the previously documented inhibition of MAO-A and/or MAO-B, increases the availability of dopamine produced by L-DOPA.

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effect of unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway on GABAA receptor subunit gene expression in the rodent basal ganglia and thalamus

Cited by 52 publications

References 34 publications

Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABAA receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion

Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABAA receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion

Glutamic Acid Decarboxylase 67 mRNA Regulation in Two Globus Pallidus Neuron Populations by Dopamine and the Subthalamic Nucleus

Locomotor effects of imidazoline I₂‐site‐specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6‐hydroxydopamine lesion of the nigrostriatal pathway

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effect of unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway on GABAA receptor subunit gene expression in the rodent basal ganglia and thalamus

Cited by 52 publications

References 34 publications

Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABAA receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion

Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABAA receptor α1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion

Glutamic Acid Decarboxylase 67 mRNA Regulation in Two Globus Pallidus Neuron Populations by Dopamine and the Subthalamic Nucleus

Locomotor effects of imidazoline I2‐site‐specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6‐hydroxydopamine lesion of the nigrostriatal pathway

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Locomotor effects of imidazoline I₂‐site‐specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6‐hydroxydopamine lesion of the nigrostriatal pathway