Different responsiveness of striatonigral and striatopallidal neurons to L‐DOPA after a subchronic intermittent L‐DOPA treatment

Carta, Annarosa; Tronci, Elisabetta; Pinna, Annalisa; Morelli, Micaela

doi:10.1111/j.1460-9568.2005.03944.x

Cited by 65 publications

(46 citation statements)

References 66 publications

(76 reference statements)

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“…L-DOPA could stimulate D 1 receptors on striatonigral neurons (Gerfen et al, 1990), so to activate the "direct" pathway (Robertson and Robertson, 1989;Carta et al, 2005), or D 1 receptors on striatonigral nerve terminals (Starr, 1987;Aceves et al, 1991). The fact that TTX prevented the L-DOPA effect rules out this latter hypothesis, although it does not exclude an intranigral action of L-DOPA because this agent could stimulate GABAergic interneurons [dendritic location of D 1 receptors has been detected in the SNr (Huang et al, 1992)].…”

Section: Neurobiological Substrates Underlying J-113397/l-dopa Interamentioning

confidence: 89%

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Marti¹,

Trapella²,

Viaro³

et al. 2007

J. Neurosci.

126

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By using a battery of behavioral tests, we showed that nociceptin/orphanin FQ receptor (NOP receptor) antagonists attenuated parkinsonian-like symptoms in 6-hydroxydopamine hemilesioned rats (Marti et al., 2005). We now present evidence that coadministration of the NOP receptor antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H benzimidazol-2-one (J-113397) and L-DOPA to 6-hydroxydopamine hemilesioned rats produced an additive attenuation of parkinsonism. To investigate the neurobiological substrates underlying this interaction, in vivo microdialysis was used in combination with behavioral measurements (bar test). J-113397 and L-DOPA alone reduced the time on bars (i.e., attenuated akinesia) and elevated GABA release selectively in the lesioned substantia nigra reticulata. J-113397 also reduced nigral glutamate levels, whereas L-DOPA was ineffective. J-113397 and L-DOPA coadministration produced additive antiakinetic effect, which was associated with additive increase in nigral GABA release but no additional reductions in glutamate levels. To investigate whether the increase in nigral GABA release could translate to changes in nigrothalamic transmission, GABA release was monitored in the ventromedial thalamus (one of the main target areas of the nigrothalamic projections). J-113397 and L-DOPA decreased thalamic GABA release and attenuated akinesia, their combination resulting in a more profound effect. These actions were prevented by perfusing the voltage-dependent Na ϩ channel blocker tetrodotoxin or the GABA A receptor antagonist bicuculline in the substantia nigra reticulata. These data demonstrate that J-113397 and L-DOPA exert their antiparkinsonian action through overinhibition of nigrothalamic transmission and suggest that NOP receptor antagonists may be useful as an adjunct to L-DOPA therapy for Parkinson's disease.

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Section: Neurobiological Substrates Underlying J-113397/l-dopa Interamentioning

confidence: 89%

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

Marti¹,

Trapella²,

Viaro³

et al. 2007

J. Neurosci.

126

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“…Altogether, these data suggest that dopamine D1/D5 receptors control GAD67 and GAD65 gene expression in striatonigral neurons via different signaling pathways. The expression of a number of transcription factors including ΔFosB or c-fos is upregulated in striatonigral neurons after systemic chronic l-DOPA or SKF-38393 administration to 6-OHDA-lesioned rats (Robertson et al, 1992;Doucet et al, 1996;Carta et al, 2005;Pavon et al, 2006;Valastro et al, 2007). Other recent studies have shown that the systemic administration of agonists of dopamine D1/D5 receptors is able to activate an extracellular-regulated kinase (ERK) pathway in striatonigral neurons in dopamine-depleted but not in intact unlesioned rats (Gerfen et al, 2002).…”

Section: Effects Of Dopamine D1/d5 Receptor Agonists On Striatonigralmentioning

confidence: 95%

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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“…Extensive studies in both rodent and nonhuman primate models, as well as studies in humans, suggest a role for the striatal opioid system in the development of LIDs (Morissette et al, 1997,Cenci et al, 1998,Duty et al, 1998,Henry et al, 1999,Johansson et al, 2001,Quik et al, 2002,Tel et al, 2002,Winkler et al, 2002,Henry et al, 2003,Carta et al, 2005,Aubert et al, 2006. Evidence for this possibility stems from results showing that enhanced PPE-B transcript levels correlate well with LIDs in experimental parkinsonian models and Parkinson's disease (Duty et al, 1998,Henry et al, 1999,Tel et al, 2002,Henry et al, 2003,Aubert et al, 2006.…”

Section: Discussionmentioning

confidence: 83%

The selective κ-opioid receptor agonist U50,488 reduces l-dopa-induced dyskinesias but worsens parkinsonism in MPTP-treated primates

Cox

Togasaki

Chen

et al. 2007

Experimental Neurology

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Several lines of evidence demonstrate that the striatal enkephalinergic system may be involved in the development of LIDs. Preproenkephalin-B (PPE-B) transcript levels are elevated with LIDs and there are also declines in κ-and other opioid receptors in different regions of the basal ganglia. If reduced κ-opioid receptors are linked to LIDs, it is possible that drugs that stimulate this subtype may decrease dyskinesias. We therefore initiated experiments to investigate the effect of κ-opioid receptor activation on LIDs. We first tested the selective κ-agonist U50,488 in rats with unilateral lesions of the nigrostriatal pathway. Chronic L-dopa treatment induced abnormal involuntary movements, including axial, orolingual and forelimb dyskinesias contralateral to the lesion. U50,488 administration prior to L-dopa treatment reduced these movements by 70%, suggesting that U50,488 has potential as an anti-dyskinetic treatment. We next tested its effect in a parkinsonian nonhuman primate model, which offers the advantage that parkinsonism and LIDs can clearly be differentiated and that the dyskinesias are similar to those in parkinsonian patients. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys were treated with L-dopa (5 mg/kg, p.o.) twice daily for 3 weeks to induce dyskinesias. As in the rodent model, U50,488 (0.1-1.0 mg/kg, i.m.) decreased LIDs in a dose-dependent fashion. However the anti-parkinsonian effect of L-dopa was similarly reduced, and side effects developed, including sedation and vomiting. These data suggest that κ-opioid agonists such as U50,488 may not be clinically useful antidyskinetic agents because they also reverse the anti-parkinsonian effect of L-dopa.

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Different responsiveness of striatonigral and striatopallidal neurons to L‐DOPA after a subchronic intermittent L‐DOPA treatment

Cited by 65 publications

References 66 publications

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

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

The selective κ-opioid receptor agonist U50,488 reduces l-dopa-induced dyskinesias but worsens parkinsonism in MPTP-treated primates

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